Kiel Life Science

Interdisciplinary Research in Life Sciences

forschung

At Kiel University, the research focus Kiel Life Science (KLS) bundles the expertise from the disciplines of bioinformatics, environmental genetics, agricultural sciences, evolutionary biology and genetics, plant breeding and animal husbandry, food sciences and evolutionary medicine. The interdisciplinary approach is also reflected in the participation of Kiel University’s most competitive faculties, research centers and major joint research projects. Common goal of all researchers involved in KLS is to advance life science research at Kiel University and to boost Kiel’s reputation as an internationally distinguished location in life sciences.

Recent publications:

Symbiosis as a tripartite relationship

Sep 25, 2019

- Joint press release by Kiel University and the GEOMAR Helmholtz Centre for Ocean Research Kiel -

Investigation of viral communities of sponges allows new insights into the mechanisms of symbiosis

Sponges form an extensive animal phylum with over 7,500 species worldwide, which occur in a wide range of habitats in the ocean. A special feature of this animal phylum is their ability to filter seawater, through which these organisms obtain their food. In doing so, certain sponge species can move up to 24,000 litres through their body per day. The surrounding seawater contains a wide range of viruses - on average, one millilitre of water contains 10 million viruses. The filter-feeding lifestyle of sponges combined with the rich proliferation of viruses in the ocean therefore might suggest that marine sponges may have a similar viral composition as the surrounding water.

Researchers from the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms" at Kiel University (CAU) and the GEOMAR Helmholtz Centre for Ocean Research Kiel have now surprisingly shown that sponges possess a very specific viral sequence signature (i.e., virome), which is remarkably unique even for the individuals of a given species. Certain bacteriophages - i.e. viruses that attack bacteria - are further able to modulate the host immune system and thus protect bacterial symbionts from being digested. While viruses are typically known for their pathogenic properties, the new research findings now also demonstrate a positive influence of bacteriophages on the interaction of host organisms with bacteria. The results were obtained through international cooperation between three countries, including researchers at the universities of Würzburg, Barcelona and Utrecht. The study published today in the renowned journal Cell Host & Microbe thus sheds new light on the symbiosis between multicellular organisms and their microbial communities, which may be regulated by bacteriophages in a tripartite relationship.

An unexplored microcosm
In order to analyse the composition of the viral community of sponges, the researchers examined four different sponge species from a defined location in the Mediterranean Sea. In each case, they compared numerous individuals and different tissues of the same species with each other. "Contrary to our original assumption, each sponge individual has its own unique virome even when living right next to each other”. Therefore, no two sponges are alike with regard to their viral community," summarised Martin T. Jahn, a doctoral researcher at GEOMAR and early career researcher at the CRC 1182. "The composition of the virome is thus not primarily determined by the environment or the exposure of the tissue to the surrounding water, but is rather defined by internal factors," said the first author of the study, who collaborated with other early career researchers from four working groups at the CRC 1182.

Notably, the viruses discovered in sponges were largely unknown. "We have found almost 500 new genera of viruses in our samples," emphasised Jahn. "These viruses are completely new, and possibly only occur in sponge, and nowhere else in nature," said Jahn. This order of magnitude shows that the study of viral diversity is only just beginning.
The animal host, bacteria and phages interact with each other
The observed differences between the viral communities of sponges and those from seawater provoked the question whether sponge viruses have specific functions. The researcher team investigated the viral gene inventories and discovered genes which are similar to those of multicellular organisms, where they are responsible for interactions of certain proteins. "This surprising result awakened our special interest," said Ute Hentschel Humeida, CRC 1182 member and professor of marine microbiology at GEOMAR. "We wanted to understand why the bacteriophages have a gene encoding a protein, which we would rather expect in multicellular organisms", continued Hentschel Humeida.

In order to investigate the role of this so-called ANKp protein, they examined its impact in a model system: they expressed the protein in the bacterium Escherichia coli and investigated its effect on certain scavenger cells (macrophages) that occur in the immune system of vertebrates. The result points to a central role of the ANKp protein: it caused E. coli to be significantly less destroyed by the scavenger cells. Strikingly, the protein apparently enables the bacteriophages to interact with the animal host in that it downregulates the host’s immune response, thereby protecting the bacteria from being digested. Therefore, the scientists suggest that bacteriophages are part of a tripartite interaction of host organism, bacteria and bacteriophages, where they provide mechanisms for maintaining symbiotic co-existence.

Extension of the symbiosis concept?
The researchers at the CRC 1182 interpret the new results as a novel and important contribution of bacteriophages to the symbioses of multicellular host organisms and their microbial partners. "We suspect that bacteriophages are major players in the interaction between multicellular host organisms - including humans - and bacteria," summarised Martin T. Jahn. "Viral proteins such as ANKp may even enable this interplay of hosts and bacteria in the first place, because they allow the bacteria to evade the immune system of the host," continued Jahn. "The fundamental concept of symbiosis can therefore be understood as an interaction between three parties," concluded Hentschel Humeida. In the future, Hentschel Humeida and team will further investigate this hypothesis, which is of central importance for metaorganism research, and confirm the functional participation of bacteriophages in host-microbe symbioses.

Original publication:
Martin T. Jahn, Ksenia Arkhipova, Sebastian M. Markert, Christian Stigloher, Tim Lachnit, Lucia Pita, Anne Kupczok, Marta Ribes, Stephanie T. Stengel, Philip Rosenstiel, Bas E. Dutilh & Ute Hentschel (2019): A phage protein aids bacterial symbionts in eukaryote immune evasion. Cell Host & Microbe Published on 24 September 2019
DOI: 10.1016/j.chom.2019.08.019

Photos are available for download at:
www.uni-kiel.de/de/pressemitteilungen/2019/283-jahn-cell-hm-sponge.jpg
Caption: The three-dimensional representation of the sponge tissue illustrates the close contact of sponge cells (red) with the bacteria (turquoise) living in the sponge.
© Martin T. Jahn, GEOMAR

www.uni-kiel.de/de/pressemitteilungen/2019/283-jahn-cell-hm-author.jpg
Caption: First author Martin Jahn, doctoral researcher at GEOMAR, examined viral composition of sponges and their participation in symbiotic interactions within the framework of the CRC 1182.
© Erik Borchert, GEOMAR

www.uni-kiel.de/de/pressemitteilungen/2019/283-jahn-cell-hm-group.jpg
Caption: Some of the CRC 1182 junior researchers that cooperated in the publication: Stephanie T. Stengel (Kiel University), Martin T. Jahn (GEOMAR), Dr. Lucia Pita (GEOMAR), Dr. Tim Lachnit (Kiel University, left to right).
© Christian Urban, Kiel University


Contact:
Prof. Ute Hentschel Humeida
Research Unit Marine Symbioses
Research Division 3: Marine Ecology
GEOMAR Helmholtz Centre for Ocean Research Kiel
Tel.: +49 (0)431 600-4480
E-mail: uhentschel@geomar.de

Martin T. Jahn
Research Unit Marine Symbioses
Research Division 3: Marine Ecology
GEOMAR Helmholtz Centre for Ocean Research Kiel
Tel.: +49 (0)431 600-4486
E-mail: mjahn@geomar.de; twitter: @martintjahn

Press contact:
Christian Urban
Science communication “Kiel Life Science"
CAU Kiel
Tel.: +49 (0)431-880-1974
E-mail: curban@uv.uni-kiel.de

More information:
Research Unit Marine Symbioses,
Research division 3: Marine Ecology
GEOMAR Helmholtz Centre for Ocean Research Kiel
www.geomar.de/de/forschen/fb3/fb3-ms/schwerpunkte/

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Did microbes assist life in colonizing land?

Sep 19, 2019

Comparative microbiome study enables researchers of the Kiel based CRC 1182 to gain new insights into the course of evolution

All living organisms exist and function only in cooperation with an abundance of symbiotic microorganisms, and have developed together with them over the course of the earth's history. This central finding of modern life sciences has led researchers worldwide to analyse the highly complex interactions and long-term bonds of host organisms and microbes in ever greater detail. Gradually, they want to achieve a new functional understanding of biology and the development of life. In the analysis of the complex interactions within the so-called metaorganism, the unit consisting of a body and the totality of its microbial colonisation, in short the microbiome, scientists use techniques such as genome sequencing. These technologies make it possible to analyse genetic information from large quantities of biological sample material and, thanks to new high-throughput methods, quickly assign it to specific organisms and, in some cases, to possible functions.

Scientists from all working groups at Kiel University involved in the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms" have now compared various sequencing techniques in an extensive comparative study using various model organisms: On the one hand to assess their optimal areas of application, and on the other hand to identify possible similarities between different multicellular host organisms and their microbiomes. A surprising result of the study presented here is that organisms living on land generally have a significantly different microbiome than species living in water. The researchers interpret this as an indication that microorganisms may have played a key role in the evolutionary transition from purely aquatic life to life on land. The new research results were published last week in the renowned scientific journal Microbiome.

The microbiome and adaptation to terrestrial life
In the new study, the scientists of the CRC 1182 used the opportunity to compare the microbiomes of many different model organisms - from simple sponges to vertebrates, including humans. They examined sample material from the various subprojects of the collaborative research project for patterns in the composition of microbial communities and compared different methods of the two most important sequencing technologies. By chance, they came across an interesting observation: the microbiome of terrestrial organisms, regardless of their kinship relationships, differs significantly from those of aquatic organisms - in which all analytical techniques coincided. Terrestrial organisms have a lower diversity of microorganisms contained in their microbiome.

A possible explanation for the differences in the composition of the microbiome could be that former aquatic organisms were forced to acquire new microbial communities upon the colonisation of the land. The transition from water to land, which began about 500 million years ago, might have been dependent on a change in the microbiome. "Just as adaptation to life on land brought about gradual, but massive morphological changes, such changes apparently also took place in the terrestrial host-associated microbiome," says John Baines, Professor for Evolutionary Genomics at Kiel University. "In order to cope with the new environmental conditions, living organisms may have resorted to terrestrially adapted microbes to maintain their vital functions," Baines continues.

Choosing the right tool
In addition to these revealing findings on a possible influence of microbiota on the course of evolution, the new CRC 1182 study also provides an aid in choosing the appropriate analytical method for the investigation of a given microbial community. On the one hand, certain sequencing methods provide only a rough identity of the microorganisms present in a sample. These comparatively inexpensive methods - such as the so-called '16s rRNA gene amplicon' method - use individual marker genes from which it is possible to deduce the associated living organisms.

More complex methods such as the so-called 'metagenomic shotgun' sequencing make it possible to record and evaluate all the genetic information in a sample. For example, they can identify individual bacterial species within the microbiome and are also able to deduce microbial functions. In comparison, however, they are more cost-intensive, their informative value depends more on the specific field of application and they are therefore currently less standardised than simpler methods.

New insights into the course of evolution
In the future, the Kiel researchers, together with their international colleagues, want to understand more precisely what role microorganisms played in the transition from an aquatic to a terrestrial way of life over the course of earth's history. "There are many indications that symbiotic microorganisms have also played a role in major evolutionary transitions," stresses CRC 1182 spokesperson Professor Thomas Bosch. "It is therefore our goal to identify the specific evolutionary mechanisms that caused the diversification of the microbiome parallel to the colonization of the land," continues Bosch.

Original publication:
Philipp Rausch, Malte Rühlemann, Britt M. Hermes, Shauni Doms, Tal Dagan, Katja Dierking, Hanna Domin, Sebastian Fraune, Jakob von Frieling, Ute Hentschel, Femke-Anouska Heinsen, Marc Höppner, Martin T. Jahn, Cornelia Jaspers, Kohar Annie B. Kissoyan, Daniela Langfeldt, Ateeqr Rehman, Thorsten B. H. Reusch, Thomas Roeder, Ruth A. Schmitz, Hinrich Schulenburg, Ryszard Soluch, Felix Sommer, Eva Stukenbrock, Nancy Weiland-Bräuer, Philip Rosenstiel, Andre Franke, Thomas Bosch, John F. Baines (2019): Comparative analysis of amplicon and metagenomic sequencing methods reveals key features in the evolution of animal metaorganisms. Microbiome Published on September 14, 2019
DOI: 10.1186/s40168-019-0743-1

Photos are available for download at:
www.uni-kiel.de/de/pressemitteilungen/2019/272-rausch-microbiome-crcmembers.JPG
Caption: Scientists from all working groups involved in the CRC 1182 contributed to the comprehensive study.
© Christian Urban, Kiel University

www.uni-kiel.de/de/pressemitteilungen/2019/272-rausch-microbiome-modelorganisms.jpg
Caption: The Kiel based researchers compared the microbiome data of many different model organisms - from simple sponges to vertebrates including humans.
© Science Communication Lab

www.uni-kiel.de/de/pressemitteilungen/2019/272-rausch-microbiome-baines.jpg
Caption: John Baines, Professor for Evolutionary Genomics at Kiel University, led the comparative microbiome study of the Collaborative Research Centre.
© Christian Urban, Kiel University

Contact:
Prof. John Baines
Institute for Experimental Medicine, Kiel University
Tel.: +49 (0) 431-500-30310
E-Mail: j.baines@iem.uni-kiel.de

Press contact:
Christian Urban
Science communication “Kiel Life Science”, Kiel University   
Tel.: +49 (0) 431-880-1974
E-Mail: curban@uv.uni-kiel.de

More Informationen:
Research Group Evolutionary Genomics, Max-Planck-Institute for Evolutionary Biology, Plön /
Kiel University:
web.evolbio.mpg.de/evolgenomics/index.html

Collaborative Research Centre 1182 „Origin and Function of Metaorganisms“, Kiel University:
www.metaorganism-research.com
 

 

 

 

Why are we different sizes?

Sep 03, 2019

Kiel research team describes the interplay of environmental factors and internal regulation in determining the growth of an organism

The body size of a living creature has a direct impact on its fitness - from the simplest animal and plant organisms right up to human beings. The individual size or height is therefore an important criterion for the ability of an organism to succeed in the competition for resources or reproduction. We basically assume that there is similar genetic information within a species, which in theory should lead to relatively uniform body sizes. However, within specific physiological limits, the individuals of most species grow to very different sizes - thus size must also be dependent on other factors. But precisely which parameters regulate growth at the molecular level has hardly been investigated to date. Now, scientists from the Zoological Institute at Kiel University (CAU) have been able to show how environmental factors and internal regulatory processes jointly control body growth, using the example of the freshwater polyp Hydra. The Kiel researchers demonstrated that the ambient temperature activates specific molecular signalling pathways of the growth process, and is thus involved in determining size. In addition, they showed that genetic factors also utilise identical signal pathways, likewise contributing to size regulation in the cnidarians. The Kiel research team recently published their new findings in the renowned scientific journal Nature Communications.

Interplay of environmental and internal regulation
From a cellular biological perspective, the size of a fully-grown organism is the result of three variables: the duration of its growth, the absolute number of the resulting cells and the individual size of all these cells, which together make up the mature organism. In the course of this characteristic growth process, the organism must be able to measure its current size, and the attainment of its maximum size. In their study, the CAU researchers initially focused on the regulation of the number of cells of the cnidarian Hydra.

"We observed that Hydra produces up to 83 percent more cells at low ambient temperatures," explained Dr Jan Taubenheim, whose doctoral research in the field of cellular and developmental biology was incorporated in the current publication. "We also managed to identify the specific molecular signalling pathways which implement the influence of the temperature on the number of cells, and thus produce larger animals at cooler temperatures," emphasised Taubenheim, who is now a research associate at the Heinrich Heine University Düsseldorf. These so-called Wnt and TGF-beta signals are involved, for example, in embryonic development and cell differentiation. Their interaction with the ambient temperature and growth in size was previously unknown. "The Wnt signals also determine the transition from growth to a stationary phase in Hydra. Therefore, we suspect that they serve the organism as a measuring instrument to determine its own size, before it stops growing," said Dr Benedikt Mortzfeld, who also obtained his doctorate in cellular biology at the CAU, and is currently employed as a research scientist at the University of Massachusetts Medical School in Worcester.

The influence of genes
In addition to the ambient temperature, certain genetic information also contribute to size regulation in cnidarians. Genes that are responsible for the so-called insulin signalling pathway jointly determine the growth, among other things by controlling the number of cells during the growth phase. In a functional gene analysis, the Kiel research team was also able to show that switching off the genes responsible for this signalling pathway led to body sizes up to 41 percent smaller in the polyps. Thus, an important role in the cellular regulation processes of growth is also played by the genetic information. "Environmental factors and genetic factors take effect one after another in a multi-step process, in a fixed hierarchical sequence, and rely on the same cellular regulatory mechanisms," summarised Professor Thomas Bosch, spokesperson of the CAU Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms". "Thus they together control cell number and size as well as the duration of the growth phase, and through their interplay facilitate great variability, which results in very different body sizes of the adult organisms," continued Bosch.

Size regulation - a common principle?
The new findings on regulating size growth in the model organism Hydra contribute towards identifying universal principles in multicellular organisms. Certain similarities in the signalling pathways lead the researchers to suspect that different organisms incorporate the influences of environment and genetics in a very similar way in their internal size regulation. The next important step will be to also investigate the influence of bacterial colonisation of the body on the underlying control processes. "We suspect that the symbiotic microorganisms of the body are also inextricably linked with the regulation of individual development and thus growth in size of an organism," said Bosch. In future, the scientists want to examine this possible involvement more closely in the framework of the CRC 1182, in order to gain a better understanding of size regulation in organisms, summarised Bosch.

Original publication:
Benedikt M. Mortzfeld*, Jan Taubenheim*, Alexander V. Klimovich, Sebastian Fraune, Philip Rosenstiel & Thomas C. G. Bosch (2019): Temperature and insulin signaling regulate body size in Hydra by the Wnt and TGF-beta pathways.
Nature Communications Published on 22 July 2019
DOI: doi.org/10.1038/s41467-019-11136-6
*Authors contributed equally

A photos is available for download at:
www.uni-kiel.de/de/pressemitteilungen/2019/261-mortzfeld-ncomms.jpg
Caption: Some specimens of the cnidarian Hydra demonstrating the effects of environmental factors and internal regulation on body growth.
© Dr. Benedikt Mortzfeld

Contact:
Prof. Thomas Bosch,
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

Press contact:
Christian Urban
Science communication “Kiel Life Science”, Kiel University  
Tel.: +49 (0)431-880-1974
E-mail: curban@uv.uni-kiel.de

More information:
AG Bosch, Kiel University:
www.bosch.zoologie.uni-kiel.de

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Stressed plants start to flower earlier

Jul 03, 2019

A botanical research team from Kiel describes the effect of certain proteins on the time of plant flowering

One of the central tasks in botanical research is the study of the plant mechanisms involved in regulating the time of flowering. All plants flower when they are transitioning from the growth stage to reproduction. The time when this transition takes place is relevant, for instance, with respect to the adaptability of plants to changing environmental conditions, especially in the context of climate change. The time of flowering is also of great importance for crop cultivation, as it determines harvest times and crop yields. The underlying processes are therefore also of great interest for breeding crops. Scientists all over the world are working intensively on investigating all of the components involved in controlling the time of flowering. A research team from the Botanical Institute at Kiel University has now characterised a previously unknown component of this regulation: taking the model plant Arabidopsis thaliana as an example, the researchers from the Department of Genetics and Molecular Biology identified a relationship between a specific protein and the time of flowering. This so-called Poco1 protein occurs in a plant cell organelle, the mitochondria, whose role in the regulation of flowering time had not been analysed in detail before. The researchers from Kiel University found out that by switching off the gene responsible for the protein, the plant starts to flower much earlier. The regulation influenced by Poco1 may also be related to unfavourable environmental conditions. The scientists, who are also actively involved in the newly founded Kiel Plant Center (KPC), published their results in the current issue of The Plant Journal, a renowned scientific publication.

An equation with many variables
The point in time when a plant changes from the so-called vegetative to the reproductive phase and begins to flower is mainly regulated by various interconnected genetic pathways. External influences such as hours of daylight or temperature also affect the time of flowering. In order to investigate the role of the Poco1 protein in this interaction, the researchers from Kiel University inactivated the Arabidopsis gene responsible for it. The plants that were modified in this way started to flower an average of five days earlier than the wild types, irrespective of the environmental conditions.

In order to confirm that this effect on the regulation of flowering time is really due to the protein, the research team carried out a number of further tests. “We took the modified plants from our experimental design and carried out a so-called genetic complementation test,” explains Hossein Emami, PhD student in the Department of Genetics and Molecular Biology. “As a result, the plants started to flower again at normal flowering time. This was another indication that the original change was due to the Poco1 protein,” Emami adds.

The comparison of root growth also points in the same direction: while in the Arabidopsis wild types a certain control mechanism stops the length growth of the roots at the transition to the reproductive phase, this signalling pathway is disturbed in the Poco1 plants. As they lack sufficient quantities of the substances contributing to this regulation, they have significantly longer roots than wild plants. “This difference compared to wild plants also seems to have been caused by the Poco1 protein,” Emami emphasises. “By downregulating the signals, this protein promotes root growth and weakens the plant’s inhibition to flower,” he adds.
Unfavourable environmental conditions affect the time of flowering.

In order to further analyse these relationships, the KPC research team investigated the interaction of mitochondria and the plant nucleus with regard to the regulation of the flowering time. They first investigated the most important physiological functions of the mitochondria and found that they were significantly disturbed in the Poco1 plants. They were found to have lower cellular respiration, a lower energy content and a higher occurrence of cell-damaging so-called free radicals in comparison with the Arabidopsis wild types. These physiological deviations are probably associated with a signal from the mitochondria to the plant nucleus, which influences the mechanism underlying earlier flowering under stress conditions.

“Unfavourable environmental conditions such as drought can cause plants to flower earlier than normal in order to ensure their reproductive success,” stresses Professor Frank Kempken, KPC member and head of the Department of Genetics and Molecular Biology. “We therefore assume that mitochondrial proteins such as Poco1 provide crucial signals and thus play a more important role in plant adaptation to environmental stress than we had previously thought,” Kempken adds. In plant breeding, these findings could be used as a basis to regulate the flowering time of important crops in such a way that they can continue to thrive even under drastically changed climatic conditions.

Original publication:
Hossein Emami and Frank Kempken (2019): PRECOCIOUS1 (POCO1), a Mitochondrial Pentatricopeptide Repeat (PPR) Protein Affects Flowering Time in Arabidopsis thaliana.
The Plant Journal Published on 20 June 2019
DOI: 10.1111/tpj.14441

Photos are available for download at:
www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/206-emami-plant-journal-authors.jpg
Caption: Lead author Hossein Emami and Professor Frank Kempken (right) have investigated the influence of mitochondrial proteins on the flowering time of Arabidopsis thaliana.
© Prof. Frank Kempken

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/206-emami-plant-journal-plants.jpg
Caption: Compared with the wild types, Poco1 plants (left) have clearly started to flower earlier.
© Prof. Frank Kempken

Contact:
Prof. Frank Kempken
Department of Genetics and Molecular Biology,
Botanical Institute and Botanic Garden, Kiel University
Tel.: +49 (0)431-880-4274
E-mail: fkempken@bot.uni-kiel.de

Press contact:
Christian Urban
Science communication “Kiel Life Science”   
Tel.: +49 (0)431-880-1974
E-mail: curban@uv.uni-kiel.de

More information:
Department of Genetics and Molecular Biology
Botanical Institute and Botanic Garden, Kiel University
http://www.uni-kiel.de/Botanik/Kempken/english.shtml

Kiel Plant Center (KPC) research centre, Kiel University:
https://www.plant-center.uni-kiel.de/en

Coincidence or master plan?

Jun 20, 2019

- Joint press release by Kiel University and the Max Planck Institute for Evolutionary Biology in Plön -

CRC 1182 research team proposes stochastic model to explain microbiome composition

All living things - from the simplest animal and plant organisms to the human body - live closely together with an enormous abundance of microbial symbionts, which colonise the insides and outsides of their tissues. The functional collaboration of host and microorganisms, which scientists refer to as a metaorganism, has only recently come into the focus of life science research. Today we know that we can only understand many of life’s processes in connection with the interactions between organism and symbionts. The Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms” at Kiel University (CAU) aims to understand the communication and the functional consequences of host-microbe relationships.



A key issue for the researchers at the CRC 1182 is how the composition of an organism’s microbiome forms during its individual development.  It is still unclear as to whether the microbial community composition is more governed by a functional selection process or if random processes dominate.  In order to examine the microbiome composition, a research team from the CAU’s CRC 1182 and the Max Planck Institute for Evolutionary Biology in Plön (MPI-EB) has now applied the theory of the so-called “neutral metaorganism” to an entire spectrum of model organisms, from very simple creatures to complex vertebrates. The scientists from Kiel and Plön published their findings yesterday in the journal PLOS Biology.

The null model of evolutionary theory

Theoretical models offer one way to make the highly complex, individual microbiome composition manageable. A fundamental model in evolutionary research is the so-called neutral null model. This is used to predict how populations would develop without any selection pressure whatsoever. The research team at the CRC 1182 has now applied this model to several model organisms from threadworms to house mice and compared the predictions with experimentally collected data. “Theory and experimental data match surprisingly well for many organisms. The predicted composition in the house mouse, for example, is found in the actual microbial species community,” summarised Dr Michael Sieber, research associate at the MPI-EB and member of the CRC 1182. “It is possible that selection plays a lesser role in the microbiome’s composition than we previously assumed, while this does not mean that the microbiome has no important functions for the organism, it could be an indication that many different compositions of the microbiome can perform these functions equally well. And which specific composition actually forms in a single organism is then driven by chance.”

A map for further exploration of the microbiome

The researchers did notice some significant deviations between the neutral model and the real compositions of the microbiome, however. For example, individual bacterial species in the mouse microbiome did not match the neutral prediction. And the microbial species composition of the Caenorhabditis elegans thread worm did not match the neutral model at all.

“We assume that these deviations between model and reality could indicate specific functions of certain microorganisms,” Sieber emphasised. Investigating the systematic deviations from the neutral model therefore holds the potential to discover key functions of certain bacterial species within the microbiome.

First explanations for the deviations from the neutral model are already being discussed. Some non-neutral bacteria in the mouse microbiome, for example, are involved in digestion and their presence may therefore be the result of a targeted selection process. On the other hand, Caenorhabditis elegans, with its very fast generational change, might not live long enough to develop a stable, mainly neutral composition of its microbiome. “The model of the neutral metaorganism therefore provides an important theoretical basis for further functional analyses of microbiome compositions across the entire spectrum of the model organisms investigated in our Collaborative Research Centre,” said CRC 1182 spokesperson Prof. Thomas Bosch.

Original publication:
Michael Sieber, Lucía Pita, Nancy Weiland-Bräuer, Philipp Dirksen, Jun Wang, Benedikt Mortzfeld, Sören Franzenburg, Ruth A. Schmitz, John F. Baines, Sebastian Fraune, Ute Hentschel, Hinrich Schulenburg, Thomas C. G. Bosch, Arne Traulsen (2019): Neutrality in the Metaorganism. PLOS Biology Published on 19 June 2019 DOI: 10.1371/journal.pbio.3000298

Photos are available for download at:

Caption: Dr Michael Sieber (left) und Prof. Arne Traulsen, Max-Planck-Institute for Evolutionary Biology, developed the Neutral Model together with researchers of the CRC 1182.
© Christian Urban, Kiel University

Caption: The scientists applied the new theoretical approach to a range of model organisms, e.g. threadworms or mice, which are investigated in the CRC 1182 at Kiel University.
© Science Communication Lab

Contact:
Dr Michael Sieber
Evolutionary Theory Department
Max Planck Institute for Evolutionary Biology in Plön
Tel.: +49 (0)4522 763-579
E-mail: sieber@evolbio.mpg.de
   
Prof. Arne Traulsen
Evolutionary Theory Department
Max Planck Institute for Evolutionary Biology in Plön
Tel.: +49 (0)4522 763-239
E-mail: traulsen@evolbio.mpg.de

Prof. Thomas Bosch,
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

Press contact:
Christian Urban
Science communication “Kiel Life Science”   
Tel.: +49 (0)431-880-1974
E-mail: curban@uv.uni-kiel.de

More information:
Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Evolutionary Theory Department,
Max Planck Institute for Evolutionary Biology in Plön:
http://web.evolbio.mpg.de/~traulsen/#home

AG Bosch, Kiel University:
http://www.bosch.zoologie.uni-kiel.de/
 

 

 

 

Intestinal microbiota defend the host against pathogens

Mar 01, 2019

Research team from the Kiel CRC 1182 examines the role of the intestinal microbiome in fighting infections, using the nematode model Caenorhabditis elegans

From single-celled organisms to humans, all animals and plants are colonised by microorganisms. As so-called host organisms, they accommodate a diverse community of symbiotic microorganisms, the microbiome, and together with them form the so-called metaorganism. The interactions between host and microbes exert a significant influence on diverse functions and health of the host organism. Scientists from the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms” at Kiel University (CAU) are investigating these complex interactions, and attribute an important role in the defence against pathogens to the microbiota. To do so, they use various experimental model organisms, i.e. living organisms which allow investigation of the interaction with their bacterial symbionts under laboratory conditions. A research team from the department of Evolutionary Ecology and Genetics at CAU has examined the function of the natural intestinal microbiome using the nematode (round worm) model Caenorhabditis elegans. They discovered that the natural C. elegans microbiome plays an important role in the defence against infections, and that certain bacteria produce a compound with a clear antimicrobial effect. In future, the results of the Kiel scientists could help to better understand the functions of the intestinal microbiome as a whole, and in particular its effects on the colonisation of the digestive tract by pathogens. Their study was published today in the scientific journal Current Biology.

Direct and indirect protection against infection
The Kiel team laid the foundation for the current research results a few years ago, when it presented the first systematic analysis of the natural worm microbiome. This investigation led to a detailed knowledge of the composition and the dominant species of the intestinal microbiome of the worm. At that time, the researchers hypothesised that the natural microbiome benefits host fitness, for example by protecting the host against pathogens. To gain a better understanding of the function of the worm microbiome, the researchers have now examined how individual bacteria from the former study affect the fitness of the host during pathogen infection. In doing so, they identified two distinct modes of action.

"On the one hand, we were able to determine a direct protective effect of certain bacteria against a pathogen," said Dr Katja Dierking, research associate in the department of Evolutionary Ecology and Genetics at CAU, and principle investigator in the CRC 1182. "Microbiota bacteria of the genus Pseudomonas inhibit the growth of the nematode specific pathogen Bacillus thuringiensis, if you put them in direct contact with each other," continued Dierking. In addition, the study of other microbiota bacteria of the genus Pseudomonas revealed an indirect effect: although they do not inhibit the growth of the pathogen directly, they nevertheless protect the worm against its harmful effects, likely through indirect, host-mediated mechanisms. The researchers found a total of six bacterial isolates in the natural microbiome which are involved in the defence against infections: two of them protect the worm directly against pathogens, and four of them indirectly.

How intestinal bacteria inhibit the growth of pathogens
Another special feature of the new Kiel study is that it not only describes the infection-inhibiting effect of individual bacteria of the worm’s microbiome, but was also able to identify an underlying molecular mechanism. Using genomic and biochemical analyses, the scientists from the Kiel CRC 1182 in collaboration with scientists from Goethe University Frankfurt were able to identify an antibacterial compound that is produced by the two Pseudomonas microbiota bacteria, which protect the worm by directly inhibiting pathogen growth. "The Pseudomonas bacteria produce a so-called cyclic lipopeptide," explained Kohar Kissoyan, first author of the study and doctoral researcher in the Evolutionary Ecology and Genetics group. "This chemical compound exerts a direct inhibitory effect on the pathogen, and thereby suppresses its further growth," continued Kissoyan.

How can we utilise the new findings?
The new results of the Kiel team establish C. elegans, which is a standard model organism studied in numerous research laboratories throughout the world, as experimental system to explore the various functions of the natural intestinal microbiome. Next, Dierking and her research team want to conduct a detailed investigation of the mechanism of action of the antibacterial compound identified in the worm’s intestinal microbiome. The goal of the CRC 1182 is to understand the interactions of the various bacteria of the microbiome with the host organism, but also with each other. In the long-term, the Kiel researchers hope that the gained knowledge will help in the development of therapeutic strategies to treat diseases related to disturbances of the intestinal microbiome, e.g. through the targeted use of probiotics, i.e. specific beneficial bacterial cultures. Currently, the Kiel metaorganisms CRC, which started in 2016, is applying for a second funding period as of 2020 at the German Research Foundation (DFG).

Original publication:
Kohar Kissoyan, Moritz Drechsler, Eva-Lena Stange, Johannes Zimmermann, Christoph Kaleta, Helge Bode and Katja Dierking (2019): Natural C. elegans microbiota protects against infection via production of a cyclic lipopeptide of the viscosin group Current Biology Published on February 28, 2019
DOI: 10.1016/j.cub.2019.01.050

Photos are available to download:
www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/058-dierking-currbio-platte.jpg
An agar plate demonstrates the inhibitory effect of Pseudomonas bacteria: The pathogen Bacillus thurigiensis cannot thrive next to them.
© Dr Sabrina Köhler

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/058-dierking-currbio-lab.jpg
Dr Katja Dierking (in the background) and Kohar Kissoyan investigated the role of C. elegans’ natural microbiome in the defence against infections.
© Dr Sabrina Köhler

Contact:
Dr Katja Dierking
Evolutionary Ecology and Genetics group, Kiel University
Tel.:     +49 (0)431-880-4145
E-mail:     kdierking@zoologie.uni-kiel.de

More information:
Department of Evolutionary Ecology and Genetics, Zoological Institute, Kiel University:
www.uni-kiel.de/zoologie/evoecogen

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Kiel University (CAU)
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban
Postal address: D-24098 Kiel, Germany, Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355 E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Twitter: www.twitter.com/kieluni
Facebook: www.facebook.com/kieluni, Instagram: www.instagram.com/kieluni

 

Selfish chromosomes make harmful fungus vulnerable to attack

Feb 12, 2019

Members of Kiel Evolution Center discover fundamentally new traits in the inheritance mechanisms of a plant-damaging fungus

Wheat is the world's second most extensively cultivated cereal crop, and in many countries an indispensable ingredient of essential staple foods. In Germany alone, 20-25 million tons of this grain are harvested per year. However, wheat cultivation in north-western Europe faces a fungal pest, which in extreme cases can cause losses of around 50 percent of the harvest: the fight against the fungus Zymoseptoria tritici is therefore of fundamental importance for food security. Disease management has so far mainly occurred in the conventional way through the widespread use of fungicides - with all the associated disadvantages for the environment and consumers. Because the fungus is becoming more resistant to fungicides and, conversely, there are no wheat varieties that are completely resistant to the pest, scientists at Kiel University (CAU) together with colleagues worldwide are intensively researching sustainable ways to keep the fungus in check.

Translational Evolutionary Research
At the CAU, the Kiel Evolution Center (KEC) in particular is working on applying evolutionary biological principles and making them usable, among other things, for pest control. An important step in this direction has now been taken by a KEC research team, together with the Max Planck Institute for Evolutionary Biology in Plön (MPI-EB), through their investigation of the basics of inheritance in this harmful fungus, and thereby also potential ways to combat it. The Kiel researchers discovered that the so-called meiosis, i.e. the maturation division of germ cells and the associated multiplication of genetic information, occurs differently in Zymoseptoria tritici than previously thought. This fungus has additional, unpaired chromosomes that can pass on genetic information to all their offspring and not just half of the following generations. "We have found that the chromosomes, but not the fungus as a whole, gain an evolutionary advantage through this type of inheritance," emphasised Dr Michael Habig, first author of the study and research associate in the Environmental Genomics group at the CAU Botanical Institute. "Only the chromosomes themselves benefit by passing on their characteristics to all descendants, and thus in a figurative sense they act egoistically," continued Habig. The researchers described this phenomenon in Zymoseptoria tritici for the first time, and recently published their results in the journal eLife.

Meiosis - an old acquaintance from biology class?
At the centre of the newly-described inheritance process is meiosis, which is a key step in sexual reproduction, and apparently takes place fundamentally differently in this fungus than previously thought. In normal so-called Mendelian inheritance, it serves to combine the different maternal and paternal chromosomes in the form of so-called homologous chromosomes, and pass these on to the descendants. In this way, the offspring inherit half of their genetic characteristics from both the mother and father. In contrast, meiosis seems to take place differently in Zymoseptoria tritici - especially regarding the so-called supernumerary chromosomes, which cannot combine with the relevant paternal or maternal counterpart. These unpaired chromosomes are thus inherited exclusively from either the mother or the father. The researchers were able to demonstrate that the maternal supernumerary chromosomes are passed on to all descendants, and not as expected only half of the descendants. "The driving force behind this strategy is the so-called meiotic drive, which ensures the increased transmission of chromosomes to the next generation," emphasised Professor Eva Stukenbrock, head of the Environmental Genomics group, which is jointly based at the CAU and the MPI-EB, and board member of the KEC. "This alternative method of inheritance was already known from other organisms. We could now prove it in Zymoseptoria tritici, and have found very many of the chromosomes involved in this meiotic drive," continued Stukenbrock.

A potential gateway to combating wheat pests
For the organism as a whole, inheritance through supernumerary chromosomes seems to be mainly a negative process. Why the fungus has nevertheless retained this in the course of evolution, over a long period of time, has not yet been fully understood. On the one hand, it inhibits the fungus’ ability to infect wheat, but on the other hand possibly increases its ability to adapt to changing environmental conditions. However, the Kiel researchers particularly see the chromosomes’ egotistical strategy as offering potential for new means of combating the harmful fungus in future. "Perhaps we will be able to introduce specific genetic information into the fungus through this special type of inheritance, which could substantially reduce its harmfulness to wheat," Habig said optimistically. "In doing so, one could take advantage of the fact that all offspring will be equipped with the corresponding genetic information," added Habig. The methods required to do this, such as so-called genome editing, are currently being intensively researched worldwide. So in future, the principle discovered at the KEC could help to permanently protect wheat plants against attack by Zymoseptoria tritici.

Original publication:
Michael Habig, Gert HJ Kema and Eva Holtgrewe Stukenbrock (2018):
Meiotic drive of female-inherited supernumerary chromosomes in a pathogenic fungus eLife
DOI: 10.7554/eLife.40251.001

Photos are available to download:
www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/039-habig-elife-blatt.jpg
A wheat leaf infested with the fungus Zymoseptoria tritici shows the typical signs of so-called leaf blotch, which can lead to drastic crop failures.
© Dr Janine Haueisen

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/039-habig-elife-infekt.jpg
Confocal microscope image of the infection of a wheat plant: the fungus penetrates the stomata of the leaves, and can spread between the plant cells.
 © Dr Janine Haueisen

Contact:
Dr Michael Habig
Environmental Genomics group
Botanical Institute, Kiel University
Tel.:     +49 (0)431-880 -6361
E-mail:     mhabig@bot.uni-kiel.de

Prof. Eva Stukenbrock
Head of the Environmental Genomics group
Botanical Institute, Kiel University
Tel.:     +49 (0)431-880 -6368
E-mail:     estukenbrock@bot.uni-kiel.de

More information:
Environmental Genomics group, Botanical Institute, Kiel University/
Max Planck Institute for Evolutionary Biology in Plön:
http://web.evolbio.mpg.de/envgen/

Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

 

 

Understanding nutrient cycling in the low-oxygen ocean

Feb 07, 2019

Joint press release by Kiel University and the GEOMAR
Helmholtz Centre for Ocean Research Kiel


Kiel research team develops basis for quantifying the nitrogen cycling in oceanic oxygen minimum zones

In the world's oceans, there are several large oxygen-depleted areas that scientists refer to as oxygen minimum zones (OMZs). These oceanic regions can encompass millions of square kilometres, and particularly occur where an intense ocean current and prevailing wind direction meet a broad coastline perpendicularly. Among other things, these flow conditions cause coastal upwelling, i.e. the upward movement of nutrient-rich deeper water. This in turn promotes the mass occurrence of oxygen-consuming microorganisms in the layers of water below the surface, which reduces the level of oxygen in the ocean. Such conditions occur, for example, in the Pacific Ocean off the west coast of South America, in line with Peru. A particularly extensive OMZ has formed here. A research team from the Collaborative Research Center 754 (SFB 754) "Climate-Biogeochemistry Interactions in the Tropical Ocean", a cooperation between Kiel University (CAU) and the GEOMAR Helmholtz Centre for Ocean Research Kiel, investigated the foraminifera, which are unicellular shell-forming microorganisms occurring throughout the ocean, in a new physiological study. Some species of foraminifera are adapted to oxygen-depleted environments as in the Peruvian OMZ. In this way, the scientists could improve our understanding of their metabolic processes, and thus extend the basis for quantifying the nitrogen cycle in the low-oxygen ocean. The researchers published their results in the journal Proceedings of the National Academy of Sciences (PNAS) yesterday.

The respiration of foraminifera
The Peruvian OMZ extends vertically from just below the water surface down to about 600 meters in depth. Depending on the depth of the water, little or no oxygen is present. These living conditions favour organisms which thrive either in the absence of oxygen or at varying levels of oxygen, such as various types of foraminifera. Depending on availability, they can "breathe" both oxygen as well as nitrate. As such, nitrate respiration goes hand in hand with the process of denitrification: this is the conversion of nitrate present in the water into molecular nitrogen in the absence of oxygen. The mass occurrence of foraminifera in the OMZ suggests that they play an important - but previously difficult to quantify - role in the nutrient cycle of these marine regions. “To better understand the role of foraminifera in the nutrient budget of the OMZ, we examined more closely the relationship between growth and denitrification rate of these organisms," explained Professor Tal Dagan from the Institute of General Microbiology at the CAU and co-author of the study.

Foraminifera prefer nitrogen to oxygen
The researchers determined the relationship between the metabolic activities of foraminifera and their size - or more precisely, the volume of their cells. In doing so they discovered that the studied OMZ foraminifera become bigger with increasing nitrate concentrations even in the absence of oxygen, and with that increasing cell volume they can also convert more nitrate. In contrast, the previous assumptions regarding the physiology of unicellular organisms with a nucleus, including foraminifera, suggested that the organisms in the OMZ should actually be smaller: with the decrease in oxygen supply, their metabolism should only be maintained with a smaller volume to surface ratio of their cells. Now, the Kiel scientists were able to resolve this contradiction: the analysed microorganisms from the OMZ do not prefer an environment with oxygen, as previously assumed. Instead, their primary metabolic pathway is nitrate respiration. "In fact, our investigations show that the foraminifera in the OMZ become bigger with increasing nitrate concentrations," said CAU marine biologist and co-author Dr Alexandra-Sophie Roy. "It seems that foraminifera do not prefer an oxygenated environment as previously assumed, or that they only switch to nitrate respiration in case of emergency. It rather seems that an environment without any oxygen is their natural preference," continued Roy.

An oxygen minimum zone in a test tube
In order to examine the metabolic pathways of the organisms, the researchers had to incubate living foraminifera in the laboratory. They obtained the organisms from sediment samples from Peruvian research area, via core sampling from the ocean floor. "Since the foraminifera in the Pacific off Peru have very specific living conditions, we had to simulate these parameters in the laboratory," said Dr Nicolaas Glock, leader of this study, from the Marine Geosystems research unit at GEOMAR, and a member of the SFB 754. "To reproduce the conditions, I worked in a cold room mimicking the ocean temperatures at 300 meters, and also precisely adjusted the salinity, nitrate and oxygen content of the experimental media”, continued Glock. He used a procedure that removes the oxygen from the seawater in a tiny glass container, a so-called cuvette, to simulate the oxygen depletion in the OMZ. He surrounded the investigated water samples containing living foraminifera with a vitamin C solution that was separated from the specimens by a thin silicon membrane. The oxygen slowly diffused through the membrane and was trapped within the Vitamin C solution. In this way, it was possible to reproduce the environmental conditions in the OMZ in the laboratory, and thereby characterise the physiological adaptations of the foraminifera to anoxia.

The influence of marine nutrient cycles on the fishing industry and climate
In the future, the theoretical basis for denitrification rates of foraminifera, described by the Kiel researchers could help to develop more accurate models of the nutrient cycles. In particular, nutrient cycling plays an important role in the oxygen minimum zones: accurate models for nutrient cycling are fundamental for our understanding of marine primary production, such as plankton growth. This in turn is the basis of the food chain in the ocean, and ultimately of all fishing yields. As such, OMZs represent only about 0.1 percent of the global ocean surface, but yield around 18 percent of global fishing. Since the OMZs may have expanded due to human influence in the last 60 years, a detailed understanding of the nutrient cycle in these regions is of particular importance. In the context of climate change, it is also becoming increasingly important to be able to quantify climate-relevant substances and their levels in the OMZs more precisely in the future. "Only with models based on realistic quantities can future predictions be made about the quantities of the important nutrient nitrate in the low-oxygen ocean, or the amount of CO2 release taking place there," said Professor Andreas Oschlies from GEOMAR, and speaker of the SFB 754. "With their newly-presented research, the scientists involved have established a very good basis for better forecasts, which now also takes into account the important role of a widespread group of organisms in the nitrogen cycle," continued Oschlies.

About the CRC 754:
The Collaborative Research Centre 754 (SFB 754) "Climate and Biogeochemical Interactions in the Tropical Ocean" was established in January 2008 as cooperation between Kiel University and the GEOMAR Helmholtz Centre for Ocean Research Kiel. The SFB 754 investigates changes in ocean oxygen content, their potential impact on oxygen minimum zones and the consequences for the global interaction of the climate and biogeochemistry of the tropical ocean. The SFB 754 is funded by the German Research Foundation (DFG) and is in its third phase (2016-2019).

Original publication:
Nicolaas Glock, Alexandra-Sophie Roy, Dennis Romero, Tanita Wein, Julia Weissenbach, Niels Peter Revsbech, Signe Høgslund, David Clemens, Stefan Sommer, Tal Dagan (2019): Metabolic preference of nitrate over oxygen as an electron acceptor in Foraminifera from the Peruvian oxygen minimum zone PNAS, Published on February 06, 2019, dx.doi.org/10.1073/pnas.1813887116

Photos are available to download:
www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-uvigerina.jpg
One of the organisms involved in the metabolic processes of the nitrogen cycle present in the oxygen minimum zone off Peru is the foraminifera species Uvigerina peregrina.
© Dr Nicolaas Glock

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-labor.jpg
Lead author Dr Nicolaas Glock from the SFB 754 conducting measurements in the laboratory of the research vessel Meteor in the South American research area.
© Prof. Tal Dagan

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-autorinnen.jpg
The scientists involved in the publication, Tanita Wein, Dr Alexandra-Sophie Roy and Dr Julia Weißenbach (from left to right) sample sediment obtained from the ocean floor off the Peruvian coast.
© Prof. Tal Dagan

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-bohrkern.jpg
The researchers obtained the foraminifera investigated from such polycarbonate core tubes taken from the Pacific seabed at a depth of approximately 500 meters.
© Prof. Tal Dagan

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-foraminiferen.jpg
Some specimens of the studied species Uvigerina striata sieved out of the sediment using sieves of various sizes.
© Prof. Tal Dagan

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-kuevettte.JPG
The researchers studied the physiology of the foraminifera in cuvettes, in which a tiny sensor measures the oxygen concentration of the water inside, among other factors.
© Prof. Tal Dagan

Contact:
Nicolaas Glock
Marine Biogeochemistry
GEOMAR Helmholtz Centre for Ocean Research Kiel
Tel.: +49 (0)431 600-2105
E-mail: nglock@geomar.de

Prof. Tal Dagan
Genomic Microbiology,
Institute of General Microbiology, Kiel University
Tel.: +49 (0)431 880-5712
E-mail: tdagan@ifam.uni-kiel.de

More information:
Collaborative Research Center (SFB) 754 "Climate-Biogeochemistry Interactions in the Tropical Ocean":
www.sfb754.de

Genomic Microbiology (Dagan working group),
Institute of General Microbiology, Kiel University:
www.mikrobio.uni-kiel.de/de/ag-dagan

Marine Geosystems research unit, GEOMAR Helmholtz Centre for Ocean Research Kiel:
www.geomar.de/forschen/fb2/fb2-mg/ueberblick/

 

Structure of a central metabolic enzyme determined

Feb 01, 2019

Kiel research team provides key to functional understanding of the human mARC1 enzyme

One of the primary challenges for every living being is to determine the usefulness or harmfulness of ingested substances. In the case of food intake, for example, highly-specialised enzymes are used, which assist with the production of energy from chemically complex food substances. On the other hand, completely different enzymes are involved in breaking down certain non-usable or toxic foreign substances: similar to the immune system, they act as a protective barrier for the body to prevent the absorption of pollutants. In contrast with the specialised digestive enzymes, they are very non-specific, since they need to respond to a wide range of different chemical compounds in order to convert these to excreta. An example of such an enzyme in the human body is the so-called mARC1, which is involved in nitrogen conversion. A Kiel research team described it for the first time around ten years ago, and suspected that it has a special significance for physiology. Now, scientists from the Institute of Pharmacy and the Centre for Biochemistry and Molecular Biology at Kiel University (CAU) have succeeded in producing a high-resolution structural image of the mARC1 enzyme, using a special X-ray crystal structure analysis. This precise depiction of its spatial structure and the molecules contained inside provides the basis for a better functional understanding of the mARC1-controlled metabolic processes. The researchers, who are part of the CAU priority research area "Kiel Life Science" (KLS), recently published their results in the scientific journal Proceedings of the National Academy of Sciences (PNAS).

The Kiel researchers suspected that the enzyme plays a significant role in the metabolism, due to its universal occurrence: it is found not only in every human being, but also in all higher forms of life throughout the animal and plant kingdom. In nitrogen conversion, it triggers biochemical processes that essentially consist of either a reaction or the corresponding reverse reaction - depending on whether it binds or releases oxygen. With these fundamental mechanisms, it can play an important role in the control of pollutants: because nitrogen compounds in some cases produce either particularly toxic or mutagenic degradation products, the enzyme can contribute to their detoxification. At the same time, mARC1 is a special case, since it is only the fourth molybdenum-containing enzyme to be identified in the human metabolism - the xenobiotic metabolism is otherwise mainly characterised by enzymes containing iron.
 
"We have now been able to look inside the active centre of mARC1 in detail for the first time, and determine how it functions on the basis of its structure," said Professor Axel Scheidig, Director of the Centre for Biochemistry and Molecular Biology (BiMo) at the CAU. "The enzyme can be very effective in reducing pollutants which accumulate in the cell as metabolic products of nitrogen conversion," continued Scheidig. However, depending on the bonds it forms, mARC1 can also work in reverse. Then a toxic effect may occur, due to the conversion caused by the enzyme.

The key to determining the detailed structure was a so-called X-ray crystal structure analysis, which the Kiel research team carried out in cooperation with colleagues from the Deutsches Elektronen-Synchrotron (DESY) in Hamburg. It allowed the very weak signal of the atomic structure itself to be amplified by X-rays, through the interaction of numerous coherently-phased molecules. In this way, the researchers were able to make the structure of the enzyme visible, using the crystal made up of billions of individual molecules. However, for successful crystallisation, they first had to clean the protein molecules of the enzyme and link them with another protein in a lengthy optimisation process, without affecting the functioning of the enzyme while doing so. "We have worked on finding a way to visualise the enzyme structure for about ten years," emphasised Scheidig. "The highly precise depiction of the detailed structure of mARC1 which is now available opens the door to potential exploitation of its functions," he continued.

Now, in further research, the whole spectrum of metabolic processes controlled by mARC1 can be explored, including the organic and inorganic compounds produced. In addition, there is also a second, very similar enzyme, mARC2, whose previously-unknown structure can now also be investigated in detail. The goal of the future work is especially to explore the therapeutic potential of the two closely-related enzymes.
 
In addition to their importance for nitrogen metabolism, the mARC enzymes are also involved in the conversion of toxic plant substances such as alkaloids, as found in plants like the common ragwort. Here too, it is possible that the chemical reaction produces both harmless and harmful degradation products. Ultimately, the targeted use of enzymes allows the development of novel medicines: for example, the enzymes are involved in the activation of newly-developed blood thinning and anti-cancer drugs. This principle also originated from the working group of Professor Bernd Clement from the Institute of Pharmacy. For future developments, it is conceivable that with the help of mARC, the conversion and thereby the activation of an active substance may be controlled so that it already works in the digestive tract, and does not first have to be absorbed into the bloodstream. Researchers also refer to such medications with delayed activation in the body as "prodrugs". "From a pharmaceutical point of view, by applying this principle, we hope for an increased effectiveness, and potentially reduced side-effects," highlighted Clement.

The genetic profile of mARC1 plays a central role in this further research: here, the Kiel scientists were able to close a knowledge gap, as previous bioinformatic methods were only able to provide an incomplete picture. "We have also identified the genes that underlie the formation of the enzyme in humans," emphasised Clement. "On this basis, we will carry out a systematic functional analysis of the mARC1 enzyme in future, using model organisms," he continued. With the targeted switching on and off of these genes using different experimental methods, comparative statements about the mode of action of the enzyme and the physiological consequences for the organism will be possible.

Original publication:
Christian Kubitza, Florian Bittner, Carsten Ginsel, Antje Havemeyer, Bernd Clement and Axel Scheidig (2018): Crystal structure of human mARC1 reveals its
exceptional position among eukaryotic molybdenum enzymes. PNAS
DOI: 10.1073/pnas.1808576115

Contact:
Prof. Axel Scheidig
Centre for Biochemistry and Molecular Biology (BiMo), CAU Kiel
Tel.:     +49 (0)431 880-4286
E-mail:    axel.scheidig@strubio.uni-kiel.de

Prof. Bernd Clement
Institute of Pharmacy, CAU Kiel
Tel.:     +49 (0)431-880-1126
E-mail:     bclement@pharmazie.uni-kiel.de

More information:
Centre for Biochemistry and Molecular Biology (BiMo), CAU Kiel
www.bimo.uni-kiel.de/de/zentrum-fuer-biochemie-und-molekularbiologie-der-christian-albrechts-universitaet-zu-kiel

Pharmaceutical Chemistry Department, Institute of Pharmacy, CAU Kiel
www.pharmazie.uni-kiel.de/chem/home.htm

Kiel University (CAU)
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban
Postal address: D-24098 Kiel, Germany, Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Jubilee: www.uni-kiel.de/cau350
Twitter: www.twitter.com/kieluni, Facebook: www.facebook.com/kieluni

 

 

 

What makes the Red Queen tick?

Jan 22, 2019

Kiel Evolution Center provides new insights into the genetic basis of evolutionary dynamics
 

"Now, here, you see, it takes all the running you can do, to keep in the same place" This advice from the Red Queen in the book "Through the Looking-Glass" by the British author Lewis Carroll serves as a metaphor for a fundamental principle in the field of evolutionary biology. The "Red Queen hypothesis", named after Carroll’s figure, states that all living organisms must constantly adapt and change, in order to survive in a constantly-changing environment. This pressure to change determines the resulting evolutionary dynamics, i.e. the ongoing reciprocal adaptations of various organisms to each other and to altered environmental conditions. Although the “Red Queen hypothesis” has been explored comprehensively at the theoretical level, to date a detailed understanding of the underlying selection mechanisms and the genes involved is still missing. A research team from the Kiel Evolution Center (KEC) at Kiel University (CAU) and the Max-Planck Institute for Evolutionary Biology (MPI) together with international colleagues, has now presented an experimental analysis of these dynamics, and the genetic information which controls this process. The researchers published their results in the current issue of the journal Proceedings of the National Academy of Sciences (PNAS).

In order to experimentally investigate the underlying evolutionary processes, the Kiel researchers focused on the coevolution of the nematode (or thread worm) Caenorhabditis elegans and its bacterial pathogen Bacillus thuringiensis. The study revealed that different factors shape coevolution in the host and pathogen: in the host, the evolutionary response is driven by changes in different genome regions at different time points. In contrast, in the pathogen, adaptation is determined by frequency changes of certain mobile genetic elements, in this case certain so-called plasmids. "The genetic processes underlying rapid host-pathogen coevolution are more complicated than previously assumed, and differ significantly in host and pathogen," said Professor Hinrich Schulenburg, head of the Evolutionary Ecology and Genetics research group at the CAU, KEC spokesperson, and also fellow at the MPI. “The Red Queen thus works differently than we thought, and in particular the role of plasmids and their frequency have not been sufficiently taken into account thus far," continued Schulenburg.

These two processes of rapid evolutionary adaptation can be illustrated using the analogy of a football game: the respective genetic make-up of the host organism and pathogen may be compared with two teams, which must adapt to compete against each other. For example, if one team has a particularly strong attack, then the other team can respond by strengthening its own defence and simply sending a larger number of defense players onto the field. In a figurative sense, this is the approach used by the pathogen, which increases the number of mobile elements, and thus improves its ability to adapt. The nematode, on the other hand, figuratively speaking, exchanges its entire team. Specifically, this means that it adapts to the pathogen though changes in different genome regions at different time points.

In order to study the reciprocal adaptation of worm and bacteria in evolution experiments, the researchers repeatedly infected populations of nematodes with a specific strain of the pathogen. The research team monitored the ensuing coevolutionary changes in the two organisms, characterizing both phenotypic as well as genetic modifications. In this context, a particularly useful characteristic of the nematode Caenorhabiditis elegans is that it survives freezing, allowing direct comparison of offspring with their ancestors - great-grandchildren and great-grandparents can thus be set in direct relationship with each other. The scientists took advantage of this particular characteristic in order to compare worms at different stages of adaptation to the pathogen. In doing so, they discovered that coevolution occurs extremely fast, within a few generations. Likewise, it also became clear that the selection pressure on the pathogens led to changes in the frequency of specific plasmids; these are responsible for the production of toxins which are harmful to the host.

The Kiel researchers believe that the results of their experiments may have uncovered a universal principle underlying rapid evolution of pathogens. Such rapid adaptive responses could be facilitated through changes in the frequency of mobile genetic elements. This is likely to apply to other pathogens, too. Diverse pathogens possess plasmids that often carry the genes for so-called virulence factors, i.e. genetic information which determines the harmfulness for the host organism. "It is possible that pathogens adapt particularly quickly to their hosts, by simply adjusting the frequency of their plasmids, or other mobile elements. New mutations are then not necessary, at least initially," explained Schulenburg. "However, this aspect has not yet been well studied, even though such frequency differences might be important for the assessment of virulence, and thus potentially also for medical diagnosis of infectious disease," concludes Schulenburg.

Original publication:
Andrei Papkou, Thiago Guzella, Wentao Yang, Svenja Koepper, Barbara Pees, Rebecca Schalkowski, Mike-Christoph Barg, Philip C. Rosenstiel, Henrique Teotónio and Hinrich Schulenburg (2018): The genomic basis of Red Queen dynamics during rapid reciprocal host pathogen coevolution PNAS

doi:10.1073/pnas.1810402116

Photos are available to download:
Bildunterschrift: Der nur etwa einen Millimeter lange Fadenwurm Caenorhabiditis elegans lässt sich ohne Schaden zu nehmen einfrieren und kann nach dem Auftauen lebendig mit seinen Nachkommen verglichen werden.
© Prof. Hinrich Schulenburg

Bildunterschrift: Der Fadenwurm lebt in wechselseitiger Anpassung an Bacillus thurigiensis-Keime (rot eingefärbt), die als Schädlinge in seinem Inneren vorkommen.
© Prof. Hinrich Schulenburg

Bildunterschrift: KEC-Sprecher Professor Hinrich Schulenburg leitete die neue Studie zu den genetischen Grundlagen der Evolutionsdynamik.
© Gunnar Dethlefsen/EvoLUNG

Contact:
Prof. Hinrich Schulenburg
Spokesperson “Kiel Evolution Center” (KEC), Kiel University
Tel.:         +49 (0)431-880-4141
E-mail:     hschulenburg@zoologie.uni-kiel.de

More information:
Department of Evolutionary Ecology and Genetics, Zoological Institute, CAU Kiel:
www.uni-kiel.de/zoologie/evoecogen

Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

Fellow group Antibiotic resistance evolution, Max-Planck Institute for Evolutionary Biology, Plön: www.evolbio.mpg.de/3248501/antibioticresistance

 

 



 
 

 
 
 

 

 

 

Cellular memory outwits pathogens

Sep 13, 2018

Study by Kiel Evolution Center proves effectiveness of sequential antibiotic treatment against the pathogen Pseudomonas aeruginosa

The World Health Organization (WHO) warns that seemingly harmless bacterial infections could develop into one of the leading causes of death in the next few years, particularly in the industrialised countries. This dramatic threat arose because, in many cases, the antibiotics that have been prescribed for decades as a standard treatment have become ineffective due to increasing resistance, and this trend continues to gather pace. The root of the problem is the germs’ rapid evolutionary adaptation to the drugs used to combat them. The consequence is that even new antibiotics can become ineffective within a short period of time. Researchers around the world are therefore pursuing an alternative approach to the worsening antibiotics crisis, in order to regain the upper hand. They are trying to prolong the effectiveness of currently available active substances, through the application of evolutionary biological principles. A research team from the Kiel Evolution Center (KEC) at Kiel University (CAU) has teamed up with colleagues at the Max Planck Institute for Evolutionary Biology in Plön and Uppsala University in Sweden to reveal a previously-unknown principle, which enables a completely new and at the same time highly sustainable form of treatment. The scientists published their results yesterday in the renowned scientific journal PNAS.

The treatment process investigated makes use of a simple principle: short-term application of a particular antibiotic is followed by another antibiotic with a different mechanism of action. Using the example of the bacterium Pseudomonas aeruginosa, which according to the WHO is one of the most critical threats of a multidrug resistant bacterium, the Kiel researchers tested the temporal alternation of antibiotics with different mechanisms of action. To do so, they examined around 200 bacterial populations in an evolution experiment over a total of 500 generations, and observed the effects of different antibiotics and various sequential treatment protocols. They discovered that the most effective sequential protocol started with a penicillin-like substance followed by a so-called aminoglycoside, especially if changes happen in short intervals.

"A short initial treatment makes the germs vulnerable, because it enables easier penetration of the bacterial cells by another drug. The second antibiotic basically finishes the job, and properly kills the remaining bacteria," explained Professor Hinrich Schulenburg, head of the Evolutionary Ecology and Genetics research group at the CAU, and KEC spokesperson. This effect is entirely dependent on the sequence of the alternating antibiotics. The sensitizing drug must be applied first, since it apparently modifies the structure of the bacterial cell walls, and thereby opens the door for the second antibiotic. In addition, the speed and the pattern of the sequence are decisive: "If we alternate the two drugs faster than in normal antibiotic treatment, and at random intervals, the then resistance evolution is inhibited most effectively," continued Schulenburg.

The reason for the success of the sequential treatment is the so-called cellular memory of the bacterial pathogens. The first antibiotic changes the cellular properties of the germs over multiple generations, to such an extent that the second antibiotic functions even better - despite being administered later. "It’s almost like the first antibiotic opens a door, which provides easier entry for the second antibiotic," explained Dr Roderich Römhild, research associate in the Evolutionary Ecology and Genetics research group, and first author of the publication. "This approach is particularly promising from an evolutionary point of view, since the pathogens are now forced to evolve a defence against opening the door - and thus against the cellular memory effect - instead of direct resistance to the antibiotic," said Römhild. In the experiment, a significant reduction in resistance was indeed confirmed.

Most surprisingly, around 30 years ago, exactly the same treatment protocol as the one proposed now was by coincidence tested on patients - with impressive results: in almost all cases, pathogen abundance was significantly reduced following the sequential antibiotic treatment; in half of the cases, the pathogens could no longer be detected, and the sequential protocol was clearly more effective than the standard treatment. However, the method never became part of medical practice, most likely because of the lack of an explanation for treatment success. "We are convinced that with our new results on the cellular memory effect, we have now found the missing explanation," emphasised Schulenburg. "The new work provides yet another example of how, with the help of evolutionary concepts and methods, we can obtain new ideas for sustainable treatment approaches," summarised the KEC spokesperson.

Original publication:
Roderich Roemhild, Chaitanya S. Gokhale, Philipp Dirksen, Christopher Blake, Philipp Rosenstiel, Arne Traulsen, Dan I. Anderson, Hinrich Schulenburg (2018): Cellular hysteresis as a principle to maximize the efficacy of antibiotic therapy PNAS doi.org/10.1073/pnas.1810004115

Photos are available to download:
A short pre-treatment with penicillin increases the effectiveness of a subsequently applied aminoglycoside. Here we see a dilution series of a bacterial sample after the end of treatment, either without (3 columns on the left) or with pre-treatment (3 columns on the right).
© Christian Urban, Uni Kiel

Dr Roderich Römhild examined the effect of sequential antibiotic treatment on the pathogen Pseudomonas aeruginosa.
© Christian Urban, Uni Kiel

Antibiotic resistance remains low, thanks to the memory effect and sequential treatment. Bacteria from the evolution experiment grown on an antibiotics gradient plate, with the concentrations increasing from left to right. Pathogens from the sequential treatment are at the bottom of the image, and have not evolved an ability to cope with high antibiotic concentrations - in contrast to the control group shown above.
© Christian Urban, Uni Kiel


Contact:
Prof. Hinrich Schulenburg
Spokesperson “Kiel Evolution Center” (KEC), Kiel University
Tel.:     +49 (0)431-880-4141
E-mail:     hschulenburg@zoologie.uni-kiel.de

More information:
Evolutionary Ecology and Genetics research group, Zoological Institute, Kiel University
www.uni-kiel.de/zoologie/evoecogen

Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

Max Planck Institute for Evolutionary Biology in Plön:
www.evolbio.mpg.de


Kiel University
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban
Postal address: D-24098 Kiel, Germany,
Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Twitter: www.twitter.com/kieluni
Facebook: www.facebook.com/kieluni, Instagram: www.instagram.com/kieluni

 

Self or nonself?

Feb 23, 2018

Why the interplay of body and microorganisms demands a redefinition of the individual

The individual is synonymous with the human personality, the smallest unit of social structures, and the central concept of existence. In order for science to define this self - which is fundamental to how we see ourselves as humans - biology has traditionally formulated three explanatory approaches, with which the human individual can be clearly set apart from their biologically active environment: the immune system, the brain and the genome make humans unique and distinguishable from all other living beings. However, in light of the new scientific field of metaorganism research, which focuses on the interaction of the organism with its microbial symbionts, this human understanding of being an individual, clearly definable self faces major challenges. Now, an interdisciplinary team of researchers from biology and anthropology, in the framework of the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms" at Kiel University, has formulated in a joint essay on why the metaorganism concept - by now broadly accepted in life sciences - demands a redefinition of the traditional concepts of the self. The ground-breaking article was published by Tobias Rees, professor of anthropology at McGill University and director at Berggruen Institute in Los Angeles, Professor Thomas Bosch, spokesperson of the Kiel CRC 1182, and Angela Douglas, professor of molecular biology and genetics at Cornell University, on Thursday 22 February in the journal PLOS Biology.

The basis of their thesis is the now-proven scientific fact that the human body is not a self-contained entity. Instead, both the development and the functioning of the human organism depend on dynamic and interactive cooperation between human and bacterial cells - or in other words, a balance in the so-called metaorganism, which comprises human and microorganisms. The proportion of bacterial cells in this system is approximately 50 percent.

This high degree of interpenetration of human and bacterial life is the reason why science must take a new look at many biological processes, in light of these multi-organismic relationships. "From the functioning of the organs, to the process of metabolism, right through to protection against infectious diseases - these new findings force us to re-examine and develop a new understanding of all life processes in our body as cooperation between humans and microorganisms," emphasised the cell and developmental biologist Bosch.

For this reason, the classical biological explanations of the individual self - the immune system, the brain and the genome - must also be re-evaluated. Defining the human self on the basis of the immune system is due, amongst other things, to its function of protecting the body against harmful external influences. Therefore, it must somehow be able to distinguish between self and nonself at the molecular level. The result is a sharp dividing line between human and non-human organism, for example in the detection and prevention of pathogens. However, it is now clear that bacteria form an essential component of the immune system: what was thus traditionally considered as part of the human self is actually largely of bacterial origin, i.e. nonself.

It is similar with the classical interpretation of the brain as the seat of core human traits like personality, self-awareness, or emotions: the bacterial colonisation of the body communicates with the nervous system, and then directly or indirectly influences cognitive processes, social behaviour and the psyche. How the brain shapes the human individual is therefore also inextricably linked to the close interconnection between organism and bacteria.

The human genome, i.e. the totality of genetic information, is considered to be unchangeable and unique to every human being. However, it has been determined that microbial genes play a major role in the manifestation of human characteristics. As the bacterial colonisation of the body is not static, the microbial genome also behaves in a highly-variable manner - in contrast with the human one. Its properties can thereby change dramatically over time, and contribute in their variability to the genetic make-up of the body. "Bacteria thus not only influence the human genome, they make up a large part of it," emphasised Rees. The definition of the human individual in terms of a fixed genetic make-up is therefore also outdated, according to Rees.

In a broader context, this revision of the human individual challenges the borders between scientific disciplines. Since the areas of human and non-human can no longer be clearly distinguished, it also calls into question the centuries-old divisions between the arts and the sciences, for example. "The era of metaorganism research is therefore not only associated with an upheaval in the life sciences," stressed Rees. "Rather, metaorganism research is an invitation to the humanities to rethink man after the nature-human separation. And that means learning to rethink human domains such as art or technology and poetry." Metaorganism research also shows how an increasingly-detailed understanding of the genetic and molecular processes of life also redefines science as a whole, added Bosch, who together with Rees is part of the interdisciplinary research programme “Humans and the Microbiome” at the Canadian Institute for Advanced Research (CIFAR).

Original publication:
Tobias Rees, Thomas Bosch, Angela E. Douglas (2018): How the microbiome challenges our concept of self. PLOS Biology
dx.doi.org/10.1371/journal.pbio.2005358 

Photos/material is available for download:
www.uni-kiel.de/download/pm/2018/2018-045-1.jpg
Caption: The traditional decoupling of man from nature, such as depicted by Caspar David Friedrich at the beginning of the 19th century, is called into question in the era of the metaorganism: the interactions of body and microorganisms define the human self.

Caspar David Friedrich, Caspar David Friedrich - Wanderer above the Sea Fog, tagged as public domain, details at  Wikimedia Commons  


Contact:
Prof. Thomas Bosch
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

More information:
Priority research area “Kiel Life Science”, Kiel University
www.kls.uni-kiel.de
 
Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Cell and Developmental Biology (Bosch AG) working group, Zoological Institute, Kiel University:
www.bosch.zoologie.uni-kiel.de

Research Program “Humans & the Microbiome”,
Canadian Institute for Advanced Research (CIFAR):
www.cifar.ca/research/humans-the-microbiome

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski
Address: D-24098 Kiel, phone: +49 (0431) 880-2104, fax: +49 (0431) 880-1355
E-Mail: ► presse@uv.uni-kiel.de, Internet: ► www.uni-kiel.de
Twitter: ► www.twitter.com/kieluni, Facebook: ► www.facebook.com/kieluni, Instagram: ► www.instagram.com/kieluni
Text / Redaktion: ► Christian Urban

Bacteria as pacemaker for the intestine

Nov 22, 2017

CAU research team discovers connection between microbiome and tissue contractions that are indispensable for healthy bowel functions

Spontaneous contractions of the digestive tract play an important role in almost all animals, and ensure healthy bowel functions. From simple invertebrates to humans, there are consistently similar patterns of movement, through which rhythmic contractions of the muscles facilitate the transport and mixing of the bowel contents. These contractions, known as peristalsis, are essential for the digestive process. With various diseases of the digestive tract, such as severe inflammatory bowel diseases in humans, there are disruptions to the normal peristalsis. To date, very little research has explored the factors underlying the control of these contractions. Now, for the first time, a research team from the Cell and Developmental Biology (Bosch AG) working group at the Zoological Institute at Kiel University (CAU) has been able to prove that the bacterial colonisation of the intestine plays an important role in controlling peristaltic functions. The scientists published their results yesterday - derived from the example of freshwater polyps - in the latest issue of Scientific Reports.

The triggers for the normal spontaneous contractions of the muscle tissue are so-called pacemaker cells of the nervous system. In a specific rhythm and without any external stimulation, they emit electrical impulses, that ultimately reach the smooth muscles of the intestinal wall, and cause them to contract. Although the impulses as such occur by themselves, their frequency and intensity, however, are subject to external influences. "The example of the simple freshwater polyp Hydra has shown us that the bacterial colonisation of the organism can affect the contractions of its digestive cavity. Most likely they do so by modulating the underlying pacemaker signals," said Professor Thomas Bosch, head of the study and spokesperson for the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms". Unlike other more complex organisms, Hydra have no bowel in the true sense of the word. Their simple body cavity assumes, amongst other things, the function of a digestive tract; the surrounding tissue also exhibits the typical contractions associated with more highly-developed intestines.

To find out how peristalsis is regulated in the freshwater polyps, the researchers compared normal Hydra which had typical bacterial colonisation with those that had their microbiome completely removed with an antibiotic cocktail. In comparison, these organisms without bacterial colonisation - also referred to as germ-free polyps - exhibited a reduction in contractions by about half. At the same time, the rhythm of the movements became disrupted, and some of the breaks between the contractions were much longer. Thus, the absence of the typical microbiome in Hydra compromised the peristaltic movements in the body cavity.

In a further step, the scientists restored the specific bacterial colonisation in the germ-free organisms. Initially, they introduced each of the five most common bacterial species found in the Hydra microbiome individually back into the sterile polyps. It turned out that this individual bacterial colonisation has no appreciable effect on the frequency and timing of contractions. Only the joint re-introduction of the five main representatives of the microbiome led to a marked improvement in peristalsis, although even then, the pattern of contractions was not fully normalised. Interestingly, an extract produced from the colonising bacteria had a similarly positive influence.

From these observation the Kiel research team concluded that only the natural Hydra microbiome - characterised by a balance between the bacterial species present - can play an important pacemaker role in peristalsis. They discovered that, in this case, certain molecules secreted by the bacteria can intervene in the control mechanism of the pacemaker cells. As such, bacterial signals can have a decisive effect on the pattern of spontaneous peristaltic contractions. "We were able to demonstrate for the first time that in our simple model organism, the microbiome has an indispensable function in the frequency and timing of tissue contractions," emphasised Bosch.

In addition, the example of the evolutionarily ancient model organism Hydra shows us that the control of vital processes of multicellular organisms by their bacterial symbionts already originated very early in the evolution of life, continued Bosch. These ground-breaking results are especially promising for medical research: "The fundamental explanation of the cooperation between organism and microbiome in regulating peristalsis will in future help us to understand the emergence of severe diseases, which arise from disrupted movement of the intestine," summarised Bosch.

Original publication:
Andrea P. Murillo-Rincón, Alexander Klimovich, Eileen Pemöller, Jan Taubenheim, Benedikt Mortzfeld, René Augustin & Thomas C.G. Bosch (2017): “Spontaneous body contractions are modulated by the microbiome of Hydra”. Scientifc Reports, Published on 21.11.2017,
doi:10.1038/s41598-017-16191-x

Photos/material is available for download:

www.uni-kiel.de/download/pm/2017/2017-368-1.gif
Caption: The typical contraction pattern of the freshwater polyp Hydra: Contraction and relaxation of the same animal over the course of three minutes.
Animation: Andrea Murillo-Rincon, Dr. Alexander Klimovich

www.uni-kiel.de/download/pm/2017/2017-368-2.jpg
Caption: Body contractions in Hydra are triggered by nerve cells (in green), while bacteria (rod-shaped cells in red) influence the underlying pacemaker activity.
Image: Christoph Giez, Dr. Alexander Klimovich

www.uni-kiel.de/download/pm/2017/2017-368-3.jpg
Caption: Hydra’s nerve cells (in green) generate electrical impulses that cause contractions of muscle fibers (shown in red) in the gastric cavity wall.
Image: Christoph Giez, Dr. Alexander Klimovich

Contact:
Prof. Thomas Bosch,
Zoological Institute, Kiel University
Tel.: 0431-880-4170
E-Mail: tbosch@zoologie.uni-kiel.de

More information:
Priority research area “Kiel Life Science”, Kiel University
www.kls.uni-kiel.de

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Cell and Developmental Biology (Bosch group), Zoological Institute, Kiel University
www.bosch.zoologie.uni-kiel.de

Plant escape from waterlogging

Oct 17, 2017

Researchers at Kiel University have discovered a previously unknown mechanism by which plant roots avoid oxygen-deficient soil

Researchers are warning about more frequently occurring extreme weather events in the future as a result of climate change. Current environmental catastrophes such as the numerous and particularly severe tropical hurricanes this year tend to confirm this trend. These extreme weather events are often accompanied by flooding, which increasingly affects agricultural land. This flooding is becoming an ever more serious problem for crop cultivation, because the majority of intensively grown crops are not very tolerant to too much water. Greater losses in yield are becoming apparent. At the same time, the pressure on the available agricultural land to produce crops is rapidly increasing in light of a growing global population.

In this context, CAU researchers in the Plant Developmental Biology and Plant Physiology research group at Kiel University’s Botanical Institute are looking at the effects of global climate change on plant growth. Using the example of a model plant that is frequently used in labs, Arabidopsis thaliana, also known as thale cress, doctoral researcher Emese Eysholdt-Derzsó investigated how plants respond to low oxygen stress that results from too much water. “In her work, Eysholdt-Derzsó describes for the first time how waterlogging and the related oxygen deficiency change the growth direction of thale cress roots and she deciphered which genetic mechanisms control the plants’ adaptation,” emphasized the head of the research group, Professor Margret Sauter. The Kiel-based research team recently published these new findings in the research journal Plant Physiology.

Soil conditions that are wet and hence low in oxygen are life-threatening for the majority of plants because they prevent the roots from growing and from absorbing nutrients. For a certain time, however, they can adapt to waterlogging with various protective mechanisms. The researchers at Kiel University have now examined how oxygen deficiency affects the growth and the overall root structure of thale cress. To do so, they exposed seven-day-old Arabidopsis seedlings to different oxygen regimes in alternation: they were confronted with low-oxygen growth conditions for a day, followed by normal conditions for a day. The experiments showed that the roots tried to escape the low-oxygen conditions by growing to the side. To do so, the plants use a genetically determined regulatory mechanism that prevents the normal, downwards root growth. Instead, the roots grow horizontally where it is more likely to reach more oxygen-rich soil areas. “We were able to show that this process is reversible. As soon as enough oxygen was available, the roots then started normal downwards growth again,” said the main author, Eysholdt-Derzsó.

The Kiel-based scientists called this entire process ‘root bending’. They were able to decipher the genetic regulation responsible for it: five of the overall 122 members of the ERF transcription factor family of thale cress are responsible for the roots responding to stress from too much water. They activate genes that ensure targeted distribution of the plant growth hormone, auxin, in the roots. As a consequence, this phytohormone is asymmetrically relocated in the root tissue. As auxin acts as an inhibitor, the root grows more slowly in places with higher concentrations of the hormone, causing the root to bend. The distribution of auxin in the root and thus the triggering of root bending can be seen with a fluorescence auxin marker.

Thale cress belongs to the crucifer plant family and is related to rapeseed or various cabbage plants. It is therefore highly likely that the findings gained from the model organism can be transferred to different crops. Future research will help to further investigate and understand the mechanism of root bending on other plants as well. The researchers’ long term goal is to possibly succeed in transferring the findings to crops, in order to increase their tolerance to waterlogging in the future and thus reduce agricultural yield losses.

This research project was financed as part of the German Research Foundation’s (DFG) single project funding.

Original publication:
Emese Eysholdt-Derzsó, Margret Sauter (2017): “Root bending is antagonistically affected by hypoxia and ERF-mediated transcription via auxin signaling”. Plant Physiology DOI:10.1104/pp.17.00555

Photos/material is available for download:

www.uni-kiel.de/download/pm/2017/2017-318-1.jpg
Caption: The lack of oxygen in the soil as a result of waterlogging causes the Arabidopsis root to bend (on the right of the image).
Image: Emese Eysholdt-Derzsó

www.uni-kiel.de/download/pm/2017/2017-318-2.jpg
Caption: Thale cress (Arabidopsis thaliana) is ideally suited as a model organism for lab experiments. Photo: Emese Eysholdt-Derzsó

www.uni-kiel.de/download/pm/2017/2017-318-3.jpg
Caption: The phyto-hormone auxin (fluorescent on the right hand edge of the image) inhibits the growth on one side and bends the Arabidopsis root.
Image: Emese Eysholdt-Derzsó

www.uni-kiel.de/download/pm/2017/2017-318-4.jpg
Caption: Emese Eysholdt-Derzsó, doctoral researcher in the Plant Developmental Biology and Plant Physiology research group at Kiel University, investigated root bending.
Photo: Christian Urban, Kiel University

www.uni-kiel.de/download/pm/2017/2017-318-5.jpg
Caption: The researchers used thale cress seedlings to investigate root bending. The seedlings were grown under controlled conditions.
Photo: Christian Urban, Kiel University

Contact:
Prof. Margret Sauter
Botanical Institute and Botanical Gardens, Kiel University
Tel.: +49 (0)431-880-4210
E-Mail: msauter@bot.uni-kiel.de

More information:
Plant Developmental Biology and Plant Physiology (Sauter research group),
Botanical Institute and Botanical Gardens, Kiel University:
www.sauter.botanik.uni-kiel.de

Priority research area “Kiel Life Science”, Kiel University:
www.kls.uni-kiel.de

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski
Address: D-24098 Kiel, phone: +49 (0431) 880-2104, fax: +49 (0431) 880-1355
E-Mail: ► presse@uv.uni-kiel.de, Internet: ► www.uni-kiel.de
Twitter: ► www.twitter.com/kieluni, Facebook: ► www.facebook.com/kieluni, Instagram: ► www.instagram.com/kieluni
Text / Redaktion: ► Christian Urban

 

Nerves control the body’s bacterial community

Sep 26, 2017

CAU research team proves, for the first time, that there is close cooperation between the nervous system and the microbial population of the body

A central aspect of life sciences is to explore the symbiotic cohabitation of animals, plants and humans with their specific bacterial communities. Scientists refer to the full set of microorganisms living on and inside a host organism as the microbiome. Over the past years, evidence has accumulated that the composition and balance of this microbiome contributes to the organism’s health. For instance, alterations in the composition of the bacterial community are implicated in the origin of various so-called environmental diseases. However, it is still largely unknown just how the cooperation between organism and bacteria works at the molecular level and how the microbiome and body exactly act as a functional unit.

An important breakthrough in deciphering these highly complex relationships has now been achieved by a research team from Kiel University’s Zoological Institute. Using the freshwater polyp Hydra as a model organism, the Kiel-based researchers and their international colleagues investigated how the simple nervous system of these animals interacts with the microbiome. They were able to demonstrate, for the first time, that small molecules secreted by nerve cells help to regulate the composition and colonisation of specific types of beneficial bacteria along the Hydra’s body column. “Up to now, neuronal factors that influence the body’s bacterial colonisation were largely unknown. We have been able to prove that the nervous system plays an important regulatory role here,” emphasises Professor Thomas Bosch, evolutionary developmental biologist and spokesperson of the Collaborative Research Centre 1182 "Origin and Function of Metaorganisms", funded by the German Science Foundation (DFG).The scientists published their new findings in Nature Communications this Tuesday.

The research team, led by Bosch, use the freshwater polyp Hydra as the model organism to elucidate the fundamental principles of nervous system structure and function. Hydra represent an evolutionary ancient branch of the animal kingdom; they have a simple body plan with a nerve net of only about 3000 neurons. Applying modern experimental technology to these organisms that, despite their simplicity, still share a large molecular similarity with the nervous systems of vertebrates, enabled identification of ancient and therefore fundamental principles of nervous system structure and function.

Using this model organism, the researchers from Kiel University addressed the question of how messenger substances produced by the nervous system, known as neuropeptides, control the cooperation and communication between host and microbes. They collected cellular, molecular and genetic evidence to show that neuropeptides have antibacterial activity which affects both the composition and the spatial distribution of the colonizing microbes.

In order to reveal the connections between neuropeptides and bacterial communities, the Kiel-based researchers first concentrated on the development of the freshwater polyp’s nervous system, from the egg stage through to an adult animal. Cnidarians develop a complete nervous system within about three weeks. During this developmental time, the bacterial communities covering the animal’s surface change radically, until a stable composition of the microbiome finally forms. Under the influence of the antimicrobial effect of the neuropeptides, the concentration of so-called Gram-positive bacteria, a subgroup of bacteria, decreases sharply over a period of roughly four weeks. At the end of the maturing process, a typical composition of the microbiome prevails, particularly dominated by Gram-negative Curvibacter bacteria. Since the neuropeptides are particularly produced in certain areas of the body only, they also control the spatial localisation of the bacteria along the body column. Thus, in the head region, for example, there is a strong concentration of antimicrobial peptides, resulting in six times fewer Curvibacter bacteria than on the tentacles.

Based on these observations, the scientists concluded that throughout the course of evolution the nervous system also participated in a controlling role for the microbiome, in addition to its sensory and motor tasks. “The findings are also important in an evolutionary context. Since the ancestors of these animals have invented the nervous system, it seems that the interaction between the nervous system and the microbiome is an ancient feature of multicellular animals. Since the simple design of Hydra has great basic and translational relevance and promises to reveal new and unexpected basic features of nervous systems, further research into the interaction between body and bacteria will therefore concentrate more on the neuronal aspects,” said Bosch, to summarise the significance of the work.

Original publication:
René Augustin, Katja Schröder, Andrea P. Murillo Rincón, Sebastian Fraune, Friederike Anton-Erxleben, Ava-Maria Herbst, Jörg Wittlieb, Martin Schwentner, Joachim Grötzinger, Trudy M. Wassenaar, Thomas C.G. Bosch (2017): “A secreted antibacterial neuropeptide shapes the microbiome of Hydra”. Nature Communications, Published on September 26, 2017, doi:10.1038/s41467-017-00625-1
 

Photos/material is available for download:

The simple structures of the freshwater polyp Hydra make it easier to research the interaction between the nervous system and the bacterial community.
Video: Priority research area "Kiel Life Science“, Kiel University

www.uni-kiel.de/download/pm/2017/2017-294-1.jpg
Caption: Nerve cells (in green) of the freshwater polyp Hydra produce antimicrobial peptides and thus shape the animal’s microbiome. Rod-shaped bacteria can be seen at the base of the tentacles, marked in red.
Image: Christoph Giez, Dr. Alexander Klimovich

www.uni-kiel.de/download/pm/2017/2017-294-2.jpg
Caption: Fibres of intestinal tissue (in red) surround the nerve cells (in green) of the freshwater polyp Hydra.
Image: Christoph Giez, Dr. Alexander Klimovich

Contact:
Prof. Thomas Bosch,
Zoological Institute, Kiel University
Tel.: 0431-880-4170
E-Mail: tbosch@zoologie.uni-kiel.de

More information:
Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Cell and Developmental Biology (Bosch group), Zoological Institute, Kiel University
www.bosch.zoologie.uni-kiel.de

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski
Address: D-24098 Kiel, phone: +49 (0431) 880-2104, fax: +49 (0431) 880-1355
E-Mail: ► presse@uv.uni-kiel.de, Internet: ► www.uni-kiel.de
Twitter: ► www.twitter.com/kieluni, Facebook: ► www.facebook.com/kieluni, Instagram: ► www.instagram.com/kieluni
Text / Redaktion: ► Christian Urban


 

Cnidarians remotely control bacteria

Sep 21, 2017

CAU research team proves for the first time that host organisms can control the function of their bacterial symbionts

In modern life sciences, a paradigm shift is becoming increasingly evident: life forms are no longer considered to be self-contained units, but instead highly-complex and functionally-interdependent communities of organisms. The exploration of the close links between multi-cellular and especially bacterial life will, in future, be the key to a better understanding of life processes as a whole, and in particular the transition between health and illness. However, how the cooperation and communication of the organisms works in detail is currently still largely unknown. An important step forward in deciphering these multi-organism relationships has now been made by researchers from the Cell and Developmental Biology working group at Kiel University’s Zoological Institute: the scientists, led by Dr. Sebastian Fraune, have been able to prove for the first time that host organisms can control not only the composition of their colonizing bacteria, but also their function. The CAU researchers published their ground-breaking findings – derived from the example of the freshwater polyp Hydra and their specific bacterial symbionts – last Monday in the latest issue of the scientific journal Proceedings of the National Academy of Sciences.

"The starting point of our investigation was the observation that Hydra can influence the composition of species-specific bacterial colonisation, by the formation of certain antimicrobial substances," explained Dr. Cleo Pietschke, lead author of the study. In principle, these simple life forms thereby manage the same task that higher-developed organisms must also accomplish to establish a healthy microbiome: using their immune system, they ensure colonisation by the "right" composition of bacteria, and must at the same time prevent useful microorganisms from having a harmful effect. The work presented focussed on how this colonisation process is supported by the communication between host and bacteria.

Once a specific population density has been reached, bacterial communities can work together in teams, in order to fulfil certain functions. The coordination of these functions is based on a sensor mechanism, with which the individual bacteria can determine total population density with the help of signal molecules. Once a threshold value is reached, these signal molecules activate genes, and thereby regulate certain cellular functions. Using this process, known as quorum sensing, bacteria control functions such as the colonisation of surfaces, or the production of toxins.

The Kiel research team has now shown that the host organism can change the quorum sensing mechanism of the bacteria. The cnidarians thereby directly influence the bacterial signal molecules, and thus actively promote the colonisation process of their own tissue. "We have found that Hydra not only influences the presence of their bacterial symbionts, but can also directly interfere with their function," emphasised Fraune, research associate in the Cell and Developmental Biology working group. The research team described in detail, for the first time, a host using quorum quenching to inhibit the molecular communication of bacteria. Previously there were only two other examples of such interventions by a host organism. Specifically, the Kiel researchers proved that a modification of certain signal molecules by the host promotes colonisation by Curvibacter, the most frequently-occurring bacteria associated with Hydra.

The CAU researchers studied the influence of the host mechanism on its bacterial community by observing the effect of a signal molecule and its host-modified bacterial counterpart. Firstly, they brought germfree Hydra, i.e. laboratory-bred organisms without bacterial colonisation, into contact with Curvibacter bacteria. It was evident that the bacterial colonisation was poor, as long as non-modified signal molecules were present. As soon as these became modified by the influence of the host organism, the bacteria colonised the body of the cnidarians to a normal extent. The researchers then repeated the experiment on organisms that already displayed bacterial colonisation. The same pattern emerged here, too: only the host-modified signal molecules encouraged consistent and typical colonisation of the Hydra by their bacterial symbionts. Further studies are required to determine how these results, obtained from cnidarian model organisms, can be applied to other life forms. However, since Hydra are primitive evolutionary organisms, it is likely that this mechanism is also similarly present in highly-developed organisms.

"At the interface between basic research and medicine, it is becoming ever clearer that the key to health lies in the balance between the body and bacterial symbionts. In the future we have the challenging task of trying to understand the highly complex relationships between hosts and bacteria. With our new findings, we are a small step closer to achieving this," said an optimistic Fraune. In Kiel, around 70 scientists are studying the multi-organismic relationships between the body and microorganisms, together in the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms".

This work was funded by the German Research Foundation (DFG) as part of the project “Host derived mechanisms controlling bacterial colonisation at the epithelial interface in the early branching metazoan Hydra (FR 3041/2-1)” and by the Cluster of Excellence "Inflammation at Interfaces” at Kiel University.

Original publication:
Cleo Pietschke, Christian Treitz, Sylvain Forêt, Annika Schultze, Sven Künzel, Andreas Tholey, Thomas C. G. Bosch and Sebastian Fraune: “Host modification of a bacterial quorum-sensing signal induces a phenotypic switch in bacterial symbionts”. Proceedings of the National Academy of Sciences, Published on September 18, 2017
doi: 10.1073/pnas.1706879114

Photos/material is available for download:

www.uni-kiel.de/download/pm/2017/2017-292-1.jpg
Caption: The freshwater polyp Hydra.
Image: Dr Sebastian Fraune

www.uni-kiel.de/download/pm/2017/2017-292-2.jpg
Caption: Electron microscopic image of the bacterial communities (Curvibacter sp.) on the surface of Hydra.
Image: Katja Schröder

Contact:
Dr Sebastian Fraune
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4149
E-Mail: sfraune@zoologie.uni-kiel.de

More information:
Dr Sebastian Fraune,
Research associate in the Cell and Developmental Biology (Bosch group),
Zoological Institute, Kiel University
www.bosch.zoologie.uni-kiel.de/?page_id=757

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Cluster of Excellence "Inflammation at Interfaces”, CAU Kiel:
www.inflammation-at-interfaces.de

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski
Address: D-24098 Kiel, phone: +49 (0431) 880-2104, fax: +49 (0431) 880-1355
E-Mail: ► presse@uv.uni-kiel.de, Internet: ► www.uni-kiel.de
Twitter: ► www.twitter.com/kieluni, Facebook: ► www.facebook.com/kieluni, Instagram: ► www.instagram.com/kieluni
Text / Redaktion: ► Christian Urban

High diversity within a simple worm

May 18, 2016

fmath-botan-inst.pngResearch team from Kiel demonstrates the importance of a natural bacterial community in one of the classical model organisms

The worm Caenorhabditis elegans is one of the best studied model organisms in biology: For decades this tiny roundworm or nematodehas been helping researchers to investigate diverse biological phenomena such as developmental processes and nervous system functions. For this work, scientists throughout the world are using a certain C. elegans strain which has been adapted to the laboratory environment and does not harbour any bacteria in its gut under these conditions. A research team from the Evolutionary Ecology and Genetics research group at Kiel University, led by Professor Hinrich Schulenburg, now demonstrated that a full appreciation of the nematode’s biology must take into account its interplay with the numerous microorganisms that live inside of the worm in nature. The Kiel researchers recently published their results on the effects of the so-called microbiome on nematode life history in the renowned journal BMC Biology.

This first systematic analysis of a natural nematode microbiome shows that the animals possess a species-rich bacterial community. Most common are Proteobacteria of the genera Pseudomonas, Stenotrophomonas or Ochrobactrum

. According to the researchers, the microbial composition is key for a more realistic view of the biology of this little worm. Their work for example showed that the natural microbiome gives the animals an evolutionary advantage and protects them against pathogens.

Even more importantly: Previously, only sterile worms were used to study various biological principles in the several hundred C. elegans

laboratories across the world. The new findings open a novel gateway into research with this worm. Scientists can now use the bacteria identified by the Schulenburg lab for their investigations in the future. "We are only at the beginning of research into the complex relationships between organisms and their associated microbes. We assume that bacteria have shaped multi-cellular life from the beginning. In future, our model will help us understand how exactly microbes influence evolution of their host organisms and in what way they determine key organismal functions such as development or immune defence against pathogens ", emphasised Schulenburg, a member of the "Kiel Life Science" research focus at Kiel University.

In order to determine the significance of the bacterial community for the worms, the researchers initially collected a total of 180 nematode samples at various sites in northern Germany, France and Portugal. The bacteria obtained from these animals were then transferred to sterile worms to study their effects on nematode life history traits. "By bringing the complex microbial community from nature into the laboratory under highly controlled conditions we can obtain a much more precise picture of the relationships between the worm as a host and its associated bacteria. This deep level of understanding would not be possible if we only studied the worms in the field", said the lead author Dr. Philipp Dirksen.

Their study approach enabled the Kiel research team to determine a central influence of the microbiome on C. elegans. The microbiome increases the fitness of the animals under normal, but also highly stressful environmental conditions. For example, worms with their microbiome are better able to produce offspring at high temperatures than sterile worms. Various Pseudomonas

bacteria also help the worms to protect themselves against fungal infections. The composition of the microbiome itself is determined by individual properties of the host, including for example their genetic characteristics. Overall worms with a natural microbiome seem to show higher fitness and reproduce at higher rates – a clear indication of an evolutionary advantage, which the bacteria provide for their host.

This new work now yields a novel and highly efficient model for the new scientific field of metaorganism research, which focusses on in-depth investigation of the interactions between organisms and their associated microorganisms. A few weeks ago the new Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms" was established on this topic at Kiel University, in which Schulenburg's research group is centrally involved.

Photos/material is available for download:
Please pay attention to our ► Hinweise zur Verwendung

Click to enlarge

The Kiel research team investigated for the first time the natural bacterial community of the roundworm Caenorhabditis elegans.
Image: Antje Thomas, Hinrich Schulenburg

Image to download:
www.uni-kiel.de/download/pm/2016/2016-152-1.gif

Click to enlarge

The bacteria (coloured orange) mainly populate the digestive tract of the roundworm.
Image: Philipp Dirksen

Image to download:
www.uni-kiel.de/download/pm/2016/2016-152-2.jpg

Click to enlarge

Lead author Dr. Philipp Dirksen investigated the composition of the nematode microbiome.
Photo: Christian Urban, Kiel University

Image to download:
www.uni-kiel.de/download/pm/2016/2016-152-3.jpg

 

www.uni-kiel.de/download/pm/2016/2016-152-4.mp4

 

Three-dimensional visualisation of the microbiome of Caenorhabditis elegans

.

Animation: Dr. Philipp Dirksen

 

Original publication:

 

Philipp Dirksen, Sarah Arnaud Marsh, Ines Braker, Nele Heitland, Sophia Wagner, Rania Nakad, Sebastian Mader, Carola Petersen, Vienna Kowallik, Philip Rosenstiel, Marie-Anne Félix and Hinrich Schulenburg (2016): The native microbiome of the nematode Caenorhabditis elegans: Gateway to a new host-microbiome model. BMC Biology

 

Link: http://dx.doi.org/10.1186/s12915-016-0258-1

 

 

Contact:

 

Prof. Hinrich Schulenburg
Arbeitsgruppe Evolutionsökologie und Genetik,
Zoologisches Institut, CAU Kiel
Tel.: +49 (0)431-880-4141
E-mail: hschulenburg@zoologie.uni-kiel.de

 

More information:

 

Department of Evolutionary Ecology and Genetics, Zoological Institute, CAU Kiel:
www.uni-kiel.de/zoologie/evoecogen/

 

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", CAU Kiel:
www.metaorganism-research.org

 

Research focus "Kiel Life Science“, CAU Kiel:
www.kls.uni-kiel.de

 

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski
Address: D-24098 Kiel, phone: +49 (0431) 880-2104, fax: +49 (0431) 880-1355
E-Mail: ► presse@uv.uni-kiel.de, Internet: ► www.uni-kiel.de
Twitter: ► www.twitter.com/kieluni, Facebook: ► www.facebook.com/kieluni
Text / Redaktion: Christian Urban

Hidden safety switch: New findings on death receptors in cancer cells

Jun 10, 2015

Achieving a better molecular understanding of the role played in the occurrence of cancer of so-called death receptors which make the progression of pancreatic cancer in particular especially aggressive and almost always fatal – this is the goal of scientists at the Institute for Experimental Tumor Research at the Christian Albrecht University of Kiel (CAU). Read more...

Live from the Evolution Lab

Jun 05, 2015

Study on coevolution between host and pathogens sheds new light on evolutionary dynamics.

 

Every year, new cold and flu pathogens occur and problematic pathogens such as Ebola cause global alarm at regular intervals. The key to a better understanding of disease epidemics lies in the adaptability and thus in the evolution of the pathogens that cause disease. With the aid of innovative experiments in the lab, researchers in the research group Evolutionary Ecology and Genetics at the Christian Albrecht University of Kiel (CAU) have now been able to gain important insights into the evolution of pathogens. Read more...

Nematode worms hitch a ride on slugs

Jul 13, 2015

Kiel scientists expand the understanding of Caenorhabditis elegans’ natural ecology


Slugs and other invertebrates provide essential public transport for small worms including Caenorhabditis elegans in the search for food, as researchers from Kiel University have now found out. These worms are around a millimeter long and commonly found in short-lived environments, such as decomposing fruit or other rotting plant material. Read more...

New strategy for fighting antibiotic-resistant pathogens

Oct 16, 2015

Daily switching of antibiotics inhibits the evolution of resistance

Rapid evolution of resistance to antibiotics represents an increasingly dramatic risk for public health. In fewer than 20 years from now, antibiotic-resistant pathogens could become one of the most frequent causes of unnatural deaths. Medicine is therefore facing the particular challenge of continuing to ensure the successful treatment of bacterial infections - despite an ever-shrinking spectrum of effective antibiotics. Recent research by a group of scientists at Kiel University has now shown that there are possible ways to prolong the effectiveness of the antibiotics that are currently available. Read more...

Marine fungi contain promising anti-cancer compounds

Oct 28, 2015

A Kiel-based research team has identified fungi genes that can develop anti-cancer compounds

To date, the ocean is one of our planet's least researched habitats. Researchers suspect that the seas and oceans hold an enormous knowledge potential and are therefore searching for new substances to treat diseases here. In the EU "Marine Fungi" project, international scientists have now systematically looked for such substances specifically in fungi from the sea, with help from Kiel University and the GEOMAR Helmholtz Centre for Ocean Research Kiel. Read more...

Why the Japanese live longer

Nov 13, 2015

Kiel-based research team shows positive influence on life span of bioactive plant compounds in green tea and soy

A research team at the Institute of Human Nutrition and Food Science at Kiel University has discovered promising links between life expectancy and two phytochemicals - the so-called catechins and isoflavones. The underlying research by the Kiel-based scientists recently appeared in the two journals Oncotarget and The FASEB Journal. Read more...

Switching mutations on and off again

Apr 12, 2016

Kiel research team facilitates functional genomics with new procedure

 

Mould is primarily associated with various health risks. However, it also plays a lesser-known role, but one which is particularly important in biotechnology. The mould (ascomycete) Aspergillus niger, for example, has been used for for around 100 years to industrially produce citric acid, which is used as a preservative additive in many foodstuffs. In order to research the genetic mechanisms which could shed light on the potential application spectrum of mould and its metabolic products, a research team from Kiel University has developed a new procedure in collaboration with colleagues from Leiden University in the Netherlands.  Read more...

New approach to antibiotic therapy is a dead end for pathogens

Jun 01, 2017

Kiel-based team of researchers uses evolutionary principles to explore sustainable antibiotic treatment strategies

The World Health Organization WHO is currently warning of an antibiotics crisis. The fear is that we are moving into a post-antibiotic era, during which simple bacterial infections would no longer be treatable. According to WHO forecasts, antibiotic-resistant pathogens could become the most frequent cause of unnatural deaths within just a few years. This dramatic threat to public health is due to the rapid evolution of resistance to antibiotics, which continues to reduce the spectrum of effective antibacterial drugs. We urgently need new treatments. In addition to developing new antibiotic drugs, a key strategy is to boost the effectiveness of existing antibiotics by new therapeutic approaches.

The Evolutionary Ecology and Genetics research group at Kiel University uses knowledge gained from evolutionary medicine to develop more efficient treatment approaches. As part of the newly-founded Kiel Evolution Center (KEC) at Kiel University, researchers under the direction of Professor Hinrich Schulenburg are investigating how alternative antibiotic treatments affect the evolutionary adaptation of pathogens. In the joint study with international colleagues now published in the scientific journal Molecular Biology and Evolution, they were able to show that in the case of the pathogen Pseudomonas aeruginosa, the evolution of resistance to certain antibiotics leads to an increased susceptibility to other drugs. This concept of so-called "collateral sensitivity" opens up new perspectives in the fight against multi-resistant pathogens.

Together with colleagues, Camilo Barbosa, a doctoral student in the Schulenburg lab, examined which antibiotics can lead to such drug sensitivities after resistance evolution. He based his work on evolution experiments with Pseudomonas aeruginosa in the laboratory. This bacterium is often multi-resistant and particularly dangerous for immunocompromised patients. In the experiment, the pathogen was exposed to ever-higher doses of eight different antibiotics, in 12-hour intervals. As a consequence, the bacterium evolved resistance to each of the drugs. In the next step, the researchers tested how the resistant pathogens responded to other antibiotics which they had not yet come into contact with. In this way, they were able to determine which resistances simultaneously resulted in a sensitivity to another drug.

The combination of antibiotics with different mechanisms of action was particularly effective - especially if aminoglycosides and penicillins were included. The study of the genetic basis of the evolved resistances showed that three specific genes of the bacterium can make them both resistant and vulnerable at the same time. "The combined or alternating application of antibiotics with reciprocal sensitivities could help to drive pathogens into an evolutionary dead end: as soon as they become resistant to one drug, they are sensitive to the other, and vice versa," said Schulenburg, to emphasize the importance of the work. Even though the results are based on laboratory experiments, there is thus hope: a targeted combination of the currently-effective antibiotics could at least give us a break in the fight against multi-resistant pathogens, continued Schulenburg.

Original publication:
Camilo Barbosa, Vincent Trebosc, Christian Kemmer, Philip Rosenstiel, Robert Beardmore, Hinrich Schulenburg and Gunther Jansen (2017): Alternative Evolutionary Paths to Bacterial Antibiotic Resistance Cause Distinct Collateral Effects. Molecular Biology and Evolution
doi.org/10.1093/molbev/msx158

Photos/material is available for download:

www.uni-kiel.de/download/pm/2017/2017-171-1.jpg
Caption: The pathogen Pseudomonas aeruginosa during the evolution experiment in the laboratory.
Image: Camilo Barbosa/Dr. Philipp Dirksen

www.uni-kiel.de/download/pm/2017/2017-171-2.jpg
Caption: Doctoral student Camilo Barbosa examined the effect of "collateral sensitivity", which can make antibiotic-resistant bacteria treatable.
Photo: Christian Urban, Kiel University

www.uni-kiel.de/download/pm/2017/2017-171-3.jpg
Caption: The research team analysed a total of 180 bacterial populations of the pathogen Pseudomonas aeruginosa.
Photo: Christian Urban, Kiel University

www.uni-kiel.de/download/pm/2017/2017-171-4.jpg
Caption: The bacteria became resistant to certain antibiotics, but at the same time sensitive to other substances.
Photo: Christian Urban, Kiel University

Contact:
Prof. Hinrich Schulenburg
Spokesperson “Kiel Evolution Center” (KEC), Kiel University
Tel.: +49 (0)431-880-4141
E-mail: hschulenburg@zoologie.uni-kiel.de

More information:
Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

Evolutionary Ecology and Genetics research group, Zoological Institute, Kiel University:
www.uni-kiel.de/zoologie/evoecogen

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski
Address: D-24098 Kiel, phone: +49 (0431) 880-2104, fax: +49 (0431) 880-1355
E-Mail: ► presse@uv.uni-kiel.de, Internet: ► www.uni-kiel.de Twitter: ► www.twitter.com/kieluni, Facebook: ► www.facebook.com/kieluni, Instagram: ► www.instagram.com/kieluni Text / Redaktion: ► Christian Urban

 

Poisonous Symbiosis

Mar 25, 2015

Scientists of Kiel University discover mechanics of poison production in Crotalaria

A working group at Kiel University (CAU) centred around Professor Dietrich Ober has discovered that symbioses between plants and bacteria are not only responsible for binding nutrients, as previously assumed, but can also be responsible for the production of plant poisons. The results were published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS).

Read more

Bacteria as pacemaker for the intestine

Nov 22, 2017

CAU research team discovers connection between microbiome and tissue contractions that are indispensable for healthy bowel functions

Spontaneous contractions of the digestive tract play an important role in almost all animals, and ensure healthy bowel functions. From simple invertebrates to humans, there are consistently similar patterns of movement, through which rhythmic contractions of the muscles facilitate the transport and mixing of the bowel contents. These contractions, known as peristalsis, are essential for the digestive process. With various diseases of the digestive tract, such as severe inflammatory bowel diseases in humans, there are disruptions to the normal peristalsis. To date, very little research has explored the factors underlying the control of these contractions. Now, for the first time, a research team from the Cell and Developmental Biology (Bosch AG) working group at the Zoological Institute at Kiel University (CAU) has been able to prove that the bacterial colonisation of the intestine plays an important role in controlling peristaltic functions. The scientists published their results yesterday - derived from the example of freshwater polyps - in the latest issue of Scientific Reports.

The triggers for the normal spontaneous contractions of the muscle tissue are so-called pacemaker cells of the nervous system. In a specific rhythm and without any external stimulation, they emit electrical impulses, that ultimately reach the smooth muscles of the intestinal wall, and cause them to contract. Although the impulses as such occur by themselves, their frequency and intensity, however, are subject to external influences. "The example of the simple freshwater polyp Hydra has shown us that the bacterial colonisation of the organism can affect the contractions of its digestive cavity. Most likely they do so by modulating the underlying pacemaker signals," said Professor Thomas Bosch, head of the study and spokesperson for the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms". Unlike other more complex organisms, Hydra have no bowel in the true sense of the word. Their simple body cavity assumes, amongst other things, the function of a digestive tract; the surrounding tissue also exhibits the typical contractions associated with more highly-developed intestines.

To find out how peristalsis is regulated in the freshwater polyps, the researchers compared normal Hydra which had typical bacterial colonisation with those that had their microbiome completely removed with an antibiotic cocktail. In comparison, these organisms without bacterial colonisation - also referred to as germ-free polyps - exhibited a reduction in contractions by about half. At the same time, the rhythm of the movements became disrupted, and some of the breaks between the contractions were much longer. Thus, the absence of the typical microbiome in Hydra compromised the peristaltic movements in the body cavity.

In a further step, the scientists restored the specific bacterial colonisation in the germ-free organisms. Initially, they introduced each of the five most common bacterial species found in the Hydra microbiome individually back into the sterile polyps. It turned out that this individual bacterial colonisation has no appreciable effect on the frequency and timing of contractions. Only the joint re-introduction of the five main representatives of the microbiome led to a marked improvement in peristalsis, although even then, the pattern of contractions was not fully normalised. Interestingly, an extract produced from the colonising bacteria had a similarly positive influence.

From these observation the Kiel research team concluded that only the natural Hydra microbiome - characterised by a balance between the bacterial species present - can play an important pacemaker role in peristalsis. They discovered that, in this case, certain molecules secreted by the bacteria can intervene in the control mechanism of the pacemaker cells. As such, bacterial signals can have a decisive effect on the pattern of spontaneous peristaltic contractions. "We were able to demonstrate for the first time that in our simple model organism, the microbiome has an indispensable function in the frequency and timing of tissue contractions," emphasised Bosch.

In addition, the example of the evolutionarily ancient model organism Hydra shows us that the control of vital processes of multicellular organisms by their bacterial symbionts already originated very early in the evolution of life, continued Bosch. These ground-breaking results are especially promising for medical research: "The fundamental explanation of the cooperation between organism and microbiome in regulating peristalsis will in future help us to understand the emergence of severe diseases, which arise from disrupted movement of the intestine," summarised Bosch.

Original publication:
Andrea P. Murillo-Rincón, Alexander Klimovich, Eileen Pemöller, Jan Taubenheim, Benedikt Mortzfeld, René Augustin & Thomas C.G. Bosch (2017): “Spontaneous body contractions are modulated by the microbiome of Hydra”. Scientifc Reports, Published on 21.11.2017,
doi:10.1038/s41598-017-16191-x

Photos/material is available for download:

www.uni-kiel.de/download/pm/2017/2017-368-1.gif
Caption: The typical contraction pattern of the freshwater polyp Hydra: Contraction and relaxation of the same animal over the course of three minutes.
Animation: Andrea Murillo-Rincon, Dr. Alexander Klimovich

www.uni-kiel.de/download/pm/2017/2017-368-2.jpg
Caption: Body contractions in Hydra are triggered by nerve cells (in green), while bacteria (rod-shaped cells in red) influence the underlying pacemaker activity.
Image: Christoph Giez, Dr. Alexander Klimovich

www.uni-kiel.de/download/pm/2017/2017-368-3.jpg
Caption: Hydra’s nerve cells (in green) generate electrical impulses that cause contractions of muscle fibers (shown in red) in the gastric cavity wall.
Image: Christoph Giez, Dr. Alexander Klimovich

Contact:
Prof. Thomas Bosch,
Zoological Institute, Kiel University
Tel.: 0431-880-4170
E-Mail: tbosch@zoologie.uni-kiel.de

More information:
Priority research area “Kiel Life Science”, Kiel University
www.kls.uni-kiel.de

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Cell and Developmental Biology (Bosch group), Zoological Institute, Kiel University
www.bosch.zoologie.uni-kiel.de

Live from the Evolution Lab

Jun 05, 2015

Study on coevolution between host and pathogens sheds new light on evolutionary dynamics.
Every year, new cold and flu pathogens occur and problematic pathogens such as Ebola cause global alarm at regular intervals. The key to a better understanding of disease epidemics lies in the adaptability and thus in the evolution of the pathogens that cause disease. With the aid of innovative experiments in the lab, researchers in the research group Evolutionary Ecology and Genetics at the Christian Albrecht University of Kiel (CAU) have now been able to gain important insights into the evolution of pathogens. To do this they examined extremely rapid, mutual adaptations of host and pathogen. The Kiel scientists have now published their results in the current edition of the prominent scientific journal PLOS Biology. Read more...

Self or nonself?

Feb 23, 2018

Why the interplay of body and microorganisms demands a redefinition of the individual

The individual is synonymous with the human personality, the smallest unit of social structures, and the central concept of existence. In order for science to define this self - which is fundamental to how we see ourselves as humans - biology has traditionally formulated three explanatory approaches, with which the human individual can be clearly set apart from their biologically active environment: the immune system, the brain and the genome make humans unique and distinguishable from all other living beings. However, in light of the new scientific field of metaorganism research, which focuses on the interaction of the organism with its microbial symbionts, this human understanding of being an individual, clearly definable self faces major challenges. Now, an interdisciplinary team of researchers from biology and anthropology, in the framework of the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms" at Kiel University, has formulated in a joint essay on why the metaorganism concept - by now broadly accepted in life sciences - demands a redefinition of the traditional concepts of the self. The ground-breaking article was published by Tobias Rees, professor of anthropology at McGill University and director at Berggruen Institute in Los Angeles, Professor Thomas Bosch, spokesperson of the Kiel CRC 1182, and Angela Douglas, professor of molecular biology and genetics at Cornell University, on Thursday 22 February in the journal PLOS Biology.

The basis of their thesis is the now-proven scientific fact that the human body is not a self-contained entity. Instead, both the development and the functioning of the human organism depend on dynamic and interactive cooperation between human and bacterial cells - or in other words, a balance in the so-called metaorganism, which comprises human and microorganisms. The proportion of bacterial cells in this system is approximately 50 percent.

This high degree of interpenetration of human and bacterial life is the reason why science must take a new look at many biological processes, in light of these multi-organismic relationships. "From the functioning of the organs, to the process of metabolism, right through to protection against infectious diseases - these new findings force us to re-examine and develop a new understanding of all life processes in our body as cooperation between humans and microorganisms," emphasised the cell and developmental biologist Bosch.

For this reason, the classical biological explanations of the individual self - the immune system, the brain and the genome - must also be re-evaluated. Defining the human self on the basis of the immune system is due, amongst other things, to its function of protecting the body against harmful external influences. Therefore, it must somehow be able to distinguish between self and nonself at the molecular level. The result is a sharp dividing line between human and non-human organism, for example in the detection and prevention of pathogens. However, it is now clear that bacteria form an essential component of the immune system: what was thus traditionally considered as part of the human self is actually largely of bacterial origin, i.e. nonself.

It is similar with the classical interpretation of the brain as the seat of core human traits like personality, self-awareness, or emotions: the bacterial colonisation of the body communicates with the nervous system, and then directly or indirectly influences cognitive processes, social behaviour and the psyche. How the brain shapes the human individual is therefore also inextricably linked to the close interconnection between organism and bacteria.

The human genome, i.e. the totality of genetic information, is considered to be unchangeable and unique to every human being. However, it has been determined that microbial genes play a major role in the manifestation of human characteristics. As the bacterial colonisation of the body is not static, the microbial genome also behaves in a highly-variable manner - in contrast with the human one. Its properties can thereby change dramatically over time, and contribute in their variability to the genetic make-up of the body. "Bacteria thus not only influence the human genome, they make up a large part of it," emphasised Rees. The definition of the human individual in terms of a fixed genetic make-up is therefore also outdated, according to Rees.

In a broader context, this revision of the human individual challenges the borders between scientific disciplines. Since the areas of human and non-human can no longer be clearly distinguished, it also calls into question the centuries-old divisions between the arts and the sciences, for example. "The era of metaorganism research is therefore not only associated with an upheaval in the life sciences," stressed Rees. "Rather, metaorganism research is an invitation to the humanities to rethink man after the nature-human separation. And that means learning to rethink human domains such as art or technology and poetry." Metaorganism research also shows how an increasingly-detailed understanding of the genetic and molecular processes of life also redefines science as a whole, added Bosch, who together with Rees is part of the interdisciplinary research programme “Humans and the Microbiome” at the Canadian Institute for Advanced Research (CIFAR).

Original publication:
Tobias Rees, Thomas Bosch, Angela E. Douglas (2018): How the microbiome challenges our concept of self. PLOS Biology
dx.doi.org/10.1371/journal.pbio.2005358 

Photos/material is available for download:
www.uni-kiel.de/download/pm/2018/2018-045-1.jpg
Caption: The traditional decoupling of man from nature, such as depicted by Caspar David Friedrich at the beginning of the 19th century, is called into question in the era of the metaorganism: the interactions of body and microorganisms define the human self.

Caspar David Friedrich, Caspar David Friedrich - Wanderer above the Sea Fog, tagged as public domain, details at  Wikimedia Commons  


Contact:
Prof. Thomas Bosch
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

More information:
Priority research area “Kiel Life Science”, Kiel University
www.kls.uni-kiel.de
 
Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Cell and Developmental Biology (Bosch AG) working group, Zoological Institute, Kiel University:
www.bosch.zoologie.uni-kiel.de

Research Program “Humans & the Microbiome”,
Canadian Institute for Advanced Research (CIFAR):
www.cifar.ca/research/humans-the-microbiome

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski
Address: D-24098 Kiel, phone: +49 (0431) 880-2104, fax: +49 (0431) 880-1355
E-Mail: ► presse@uv.uni-kiel.de, Internet: ► www.uni-kiel.de
Twitter: ► www.twitter.com/kieluni, Facebook: ► www.facebook.com/kieluni, Instagram: ► www.instagram.com/kieluni
Text / Redaktion: ► Christian Urban

Hidden safety switch: New findings on death receptors in cancer cells

Jun 10, 2015

Achieving a better molecular understanding of the role played in the occurrence of cancer of so-called death receptors which make the progression of pancreatic cancer in particular especially aggressive and almost always fatal – this is the goal of scientists at the Institute for Experimental Tumor Research at the Christian Albrecht University of Kiel (CAU). The working group headed up by Professor Anna Trauzold and Professor Holger Kalthoff has been working for more than ten years now on these death receptors which can cause the controlled death of the cell, the programmed cell death, in almost all body cells and, in principle, also in cancer cells. Read more...

Conquering the Extreme

Credit: ESO/G. Beccari, License: CC BY 4.0, http://www.eso.org/public/images/eso1723a/

May 04, 2018

How microorganisms support multicellular organisms with the colonisation of hostile environments

From hot and nutrient-poor deserts to alternating dry and wet intertidal zones, right through to the highest water pressure and permanent darkness in the deep sea: in the course of its development over millions of years, life has conquered even the most extreme places on earth. That termites can live off indigestible wood, plants can exist in deserts - seemingly without water and nutrients, or sea anemones can tolerate the constant change between underwater and dry environments in intertidal zones, apparently also depends on close cooperation with their bacterial symbionts. Life scientists around the world are currently investigating the manner in which the symbiotic interaction of microorganisms and hosts, in the functional unit of a metaorganism, supports the colonisation of such extreme habitats. An international research team under the leadership of the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms” at Kiel University has now presented an inventory of mechanisms, with which the interactions of hosts and symbionts support life under extreme environmental conditions, or even make it possible at all. Together with colleagues from Saudi Arabia’s King Abdullah University of Science and Technology (KAUST), the researchers have now described in detail for the first time in the scientific journal Zoology how microorganisms can promote the growth and the evolutionary fitness of different organisms in extreme locations.

An important factor in response to changing living conditions is time. If the environment at a particular place changes very quickly, for example through drastic change in physical and chemical conditions such as light or oxygen levels, the more highly-developed multicellular organisms in particular find the adjustment difficult. Their ability to adapt is too slow, because the required genetic change can only be completed over the course of several generations. "Here microorganisms can give their host organisms an advantage," emphasised Professor Thomas Bosch, cell and developmental biologist at Kiel University and spokesperson for the CRC 1182. "With bacteria, for example, the evolutionary processes occur much more rapidly. They can partially transfer this ability to respond much faster to environmental changes to their hosts, and thereby assist the hosts with adaptation," continued Bosch. 

The lack of food or the inability to actually use the available nutrients further limits the available habitats. The metabolisms of many organisms are geared to specific optimal living conditions, and struggle to cope in extreme areas. Here too, it is often the symbiotic relationships with bacteria which enable plants and animals to expand the functioning of their own metabolisms. Thus, different organisms can, for example, exchange nutrients with their bacterial partners, and thereby utilise food sources which their metabolisms otherwise could not process. 

Certain symbiotic bacteria, which colonise the roots of plants, help them to absorb elements such as nitrogen and other minerals in dry and nutrient-poor locations. Other bacteria support plant growth by increasing tolerance to saline soil. In the future, researchers will focus on investigating such helpful bacterial cultures, regarding their applicability to crops. Potentially, a better understanding of plants as metaorganisms could also help to utilise previously-unusable deserts for agriculture in the future.

In addition, microbial symbionts enable various organisms to develop a high tolerance towards a rapidly-changing environment: fixed cnidarians in the inter-tidal zones of different oceans can, for example, quickly adapt to the extreme changes in their living conditions because they can also abruptly change the composition of their bacterial colonisation. Behind this lie mechanisms such as the direct exchange of genetic information between different bacterial species, which controls the exclusion or inclusion of specific types of bacteria in the metaorganism. "In sea anemones, their bacterial colonisation changes in accordance with the prevailing site conditions," emphasised Dr Sebastian Fraune, research associate at the Zoological Institute at Kiel University. "The organisms can potentially save this flexible bacterial configuration, and recall it in the event of a change in their habitat, in order to cope with the new conditions," continued Fraune.

From the investigation of this bacterial-controlled ability to adapt to fast-changing environmental conditions, it may be possible in future to draw conclusions about the effects of climate change on organisms and ecosystems, or even to deduce adaptation strategies. Further research will clarify how the health and fitness of a metaorganism depend on the adaptability of its individual partners, and what effects arise from changing individual elements of this complex structure. The new findings thus emphasise the fundamental importance of researching the multi-organismic relationships between hosts and microorganisms, in particular, too, for the understanding of life in a variable and extreme environment.


Original publication:
Corinna Bang, Tal Dagan, Peter Deines, Nicole Dubilier, Wolfgang J. Duschl, Sebastian Fraune, Ute Hentschel, Heribert Hirt, Nils Hülter, Tim Lachnit, Devani Picazo, Lucia Pita, Claudia Pogoreutz, Nils Rädecker, Maged M. Saad, Ruth A. Schmitz, Hinrich Schulenburg, Christian R. Voolstra, Nancy Weiland-Bräuer, Maren Ziegler, Thomas C.G. Bosch (2018): Metaorganisms in extreme environments: do microbes play a role in organismal adaptation? Biology doi.org/10.1016/j.zool.2018.02.004


A photo is available for download under:
www.uni-kiel.de/download/pm/2018/2018-131-1.jpg 
Associated microbiota can promote the host’s vigour and proliferation in extreme environments. Such insights may be informative even when attempting to remotely detect the presence of life in extreme conditions on terrestrial planets. The Photograph shows the spectacular Orion Nebula, 
taken by ESO’s VLT Survey Telescope (VST).
Credit: ESO/G. Beccari, License: CC BY 4.0, http://www.eso.org/public/images/eso1723a/ 

Contact:
Prof. Thomas Bosch
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

More information:
Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

KAUST news release on the related „Metaorganism Frontier Research Workshop“:
www.kaust.edu.sa/en/news/exploring-the-metaorganism-frontier


Christian-Albrechts-Universität zu Kiel
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban 
Postal address: D-24098 Kiel, Germany, Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Twitter: www.twitter.com/kieluni 
Facebook: www.facebook.com/kieluni, Instagram: www.instagram.com/kieluni

 

Nematode worms hitch a ride on slugs

Jul 13, 2015

2015-263-1.jpgKiel scientists expand the understanding of Caenorhabditis elegans’ natural ecology


Slugs and other invertebrates provide essential public transport for small worms including Caenorhabditis elegans in the search for food, as researchers from Kiel University have now found out. These worms are around a millimeter long and commonly found in short-lived environments, such as decomposing fruit or other rotting plant material. Read more...

What the metabolism reveals about the origin of life

May 07, 2018

Kiel botanist proposes new theory for the simultaneous evolution of opposing metabolic processes

Which came first, the chicken or the egg? This classical ‘chicken-or-egg’ dilemma applies in particular to the developmental processes of life on earth. The basis of evolution was a gradual transition from purely chemical reactions towards the ability of the first life forms to convert carbon via metabolic processes, with the help of enzymes. In this transition, early life forms soon developed different strategies for energy production and matter conversion. 

In principle, science distinguishes between so-called heterotrophic and autotrophic organisms: the first group, which includes all animals for example, uses various organic substances as energy sources. Their metabolic processes produce CO2 - amongst other things - during respiration. In contrast, autotrophic organisms exclusively use inorganic carbon compounds for their metabolism. This group includes all plants, which carry out photosynthesis and thereby bind CO2 to gain energy from sunlight.

In evolution research, scientists around the world have long discussed which of the two basic metabolic strategies developed first - autotrophy or heterotrophy, i.e. photosynthesis or respiration. Dr Kirstin Gutekunst, research associate in the Plant Cell Physiology and Biotechnology Group at the Botanical Institute at Kiel University, proposes instead that both developments may have occurred simultaneously and in parallel. The Kiel botanist presents this novel theory for discussion, which she has titled "Hypothesis on the Synchronistic Evolution of Autotrophy and Heterotrophy", in the journal Trends in Biochemical Sciences.

Gutekunst argues as follows: in terms of matter conversion, the earth represents a closed system. The quantity of every kind of matter on earth cannot be changed - it is only continuously converted and reassembled. There must therefore be a balance in such a system - otherwise certain substances would be permanently removed and others permanently added. The logical conclusion is that for every metabolic process, there must be a corresponding opposing process - either within the same organism, or in two different organisms which have opposing metabolic processes. A third core argument of the new hypothesis lies in the fact that the main drivers of the metabolism, the enzymes, can inherently act in two directions - so therefore, every metabolic reaction can be reversed by the corresponding opposing reaction. Metabolic processes overall are not linear, but rather cyclical, and have a global balance of materials.

"The current scientific knowledge suggests that heterotrophy and autotrophy cannot have developed independently of each other. In a closed system that is characterised by a balance of materials, then both metabolic processes are interdependent," said Kirstin Gutekunst. "Just like neither the chicken nor the egg could have originated first, so too heterotrophic and autotrophic organisms cannot have developed after each other," continued the Kiel plant researcher. An example of this kind of balance of materials can be found in cyanobacteria, also known as blue-green algae. They combine the metabolic processes of photosynthesis and respiration in one organism, and thus display heterotrophic and autotrophic properties at the same time. Here, these processes are particularly closely linked, and are based on identical molecular components.

The new theory of the Kiel researcher could thus provide impetus to re-evaluating the existing conception of the origin of life on earth in future. In principle, the question of origin can only be viewed hypothetically. However, Gutekunst’s theory offers credible indices against the idea of a singular origin, which in essence is technically based on an unscientific idea of creation. In contrast, the proposed synchronistic hypothesis suggests a duality right from the beginning of evolution. If metabolic processes based on the effect of enzymes are acknowledged as a characteristic of life, then for each reaction there must also be an opposing reaction. Such an evolution can therefore only have started at the same time, and from there onwards developed in parallel. Gutekunst’s thesis is thus a strong argument against the assumption of a singular origin of autotrophy or heterotrophy.

The publication forms part of the plant research conducted within the priority research area "Kiel Life Science" at Kiel University. Currently, the scientists in this area are striving to network with each other better, and to encourage mutual exchange of ideas and information. In this context, together with partner institutions in the region, they are preparing the formation of an independent, interdisciplinary centre for plant research at Kiel University.

Original publication:
Kirstin Gutekunst (2018): Hypothesis on the Synchronistic Evolution of Autotrophy and Heterotrophy Trends in Biochemical Sciences
doi.org/10.1016/j.tibs.2018.03.008

Photos are available to download:
www.uni-kiel.de/download/pm/2018/2018-134-1.jpg 
Caption: The Hypothesis on the Synchronistic Evolution of Autotrophy and Heterotrophy assumes that the opposing processes must have developed at the same time.    
Image: Dr Kirstin Gutekunst

Contact:
Dr Kirstin Gutekunst
Plant Cell Physiology and Biotechnology Group,
Botanical Institute and Botanical Gardens, Kiel University
Tel.:         +49 (0)431-880-4237
E-mail:     kgutekunst@bot.uni-kiel.de

More information:
Plant Cell Physiology and Biotechnology Group,
Botanical Institute and Botanical Gardens, Kiel University
www.biotechnologie.uni-kiel.de

Priority research area “Kiel Life Science”, Kiel University
www.kls.uni-kiel.de

Christian-Albrechts-Universität zu Kiel
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban
Postal address: D-24098 Kiel, Germany, Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de
Twitter: www.twitter.com/kieluni, Facebook: www.facebook.com/kieluni

 

New strategy for fighting antibiotic-resistant pathogens

Oct 16, 2015

Daily switching of antibiotics inhibits the evolution of resistance

Rapid evolution of resistance to antibiotics represents an increasingly dramatic risk for public health. In fewer than 20 years from now, antibiotic-resistant pathogens could become one of the most frequent causes of unnatural deaths. Medicine is therefore facing the particular challenge of continuing to ensure the successful treatment of bacterial infections - despite an ever-shrinking spectrum of effective antibiotics. Recent research by a group of scientists at Kiel University has now shown that there are possible ways to prolong the effectiveness of the antibiotics that are currently available. Read more...

Cancer diagnosis: no more needles?

May 25, 2018

Kiel University research team proposes extracting genetic material for research and diagnostic purposes from urine in future

Urine is an everyday liquid which most people pay little attention to and regard as rather unpleasant. It’s quite the opposite for a group of clinical researchers from Kiel University, the University Medical Center Schleswig-Holstein (UKSH) and the Lithuanian University of Health Sciences in Kaunas, who are convinced of the diagnostic potential of this yellowish liquid. The reason for this is the genetic material that urine contains – especially the so-called cell-free DNA - which offers new opportunities for cancer diagnostics. The researchers in the lab were able to extract just as much as cell-free DNA from 60 ml of urine (about half a urine beaker) as from a 10 ml blood sample. The research team is working on developing new procedures to extract cell-free DNA from urine for this purpose. Together with their international colleagues, the researchers from the Institute of Clinical Molecular Biology (IKMB) at Kiel University have now published their findings today in the current issue of the journal BioTechniques.

The term cell-free DNA refers to fragments of genetic information that are found outside of cells in various bodily fluids. These DNA components originate when body cells die - but also when tumour cells die. They are initially released into the bloodstream, and from there also make their way into the urine. The research team initially encountered a series of problems: the amount of DNA in urine differs greatly from person to person, and even varies significantly in the same person from day to day. This meant that the DNA concentrations in the samples were initially sometimes too low, so that the researchers had to increase the respective quantities of urine collected. They also regularly observed that the urine of healthy women contains more than twice as much cell-free DNA than the identical amount of urine in healthy men. This factor must be taken into account in future cancer diagnostics, so that these gender-specific differences do not distort the results. 

To date, tests for diagnosing cancer are mostly based on blood samples. Some of these blood tests use cell-free DNA, which may originate from a possible tumour, to identify certain types of lung and colon cancer. In the next twelve months, the scientists plan to carry out further research in the IKMB laboratory at Kiel University, to determine whether genetic material from urine is as suitable for clinical research and diagnostics as blood.  "To do so, we will examine available samples from study participants at the University Medical Centre, and compare the genetic traces of a tumour in the blood plasma and urine to determine whether both methods can reliably detect the disease," said Michael Forster, a scientist at the Institute of Clinical Molecular Biology at Kiel University.

In future, the researchers in Kiel hope to develop a urine-based test which is as reliable as traditional blood tests. This would primarily benefit patients, who would be spared the unpleasant blood withdrawal. In addition, such a test procedure would be faster and less expensive than the previous methods - for example, unlike with blood tests, no medical personnel are required when taking urine samples. "In the United States, a similar test procedure is already commercially available for cancer research. Recently, an international research team also presented a new urine test, which has not yet been clinically approved, for certain tumours in the urinary tract," said Forster regarding the current state of progress. "The introduction of new urine-based clinical tests in Germany still requires several years of clinical research, as well as further cost/benefit analysis," continued the molecular geneticist.

The follow-up research will be carried out in cooperation with external clinical research groups, within the framework of the new Competence Centre for Genome Analysis Kiel (CCGA Kiel). The CCGA Kiel is Germany's largest academic high-throughput sequencing centre. It has received funding from the German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF). Operating one of the four newly-created sequencing super-centres in Germany, Kiel University is servicing the exploding demand for complex genome analysis in the life sciences,.

Original publication:
Greta Streleckiene, Hayley M Reid, Norbert Arnold, Dirk Bauerschlag, Michael Forster (2018): Quantifying cell free DNA in urine: comparison between commercial kits, impact of gender and inter-individual variation BioTechniques DOI: 10.2144/btn-2018-0003

Photos are available to download:
www.uni-kiel.de/download/pm/2018/2018-165-1.jpg
The Kiel University research team would like to use urine instead of blood in future for cancer diagnosis. 
Photo: Christian Urban, Kiel University

www.uni-kiel.de/download/pm/2018/2018-165-1.jpg
The leader of the study, Michael Forster, together with his colleagues Regina Fredrik (left) and Nicole Braun from the Institute of Clinical Molecular Biology at Kiel University.
Photo: Christian Urban, Kiel University

Contact:
Michael Forster
Institute of Clinical Molecular Biology, Kiel University 
Tel.: +49 (0)431-500-15136
E-mail: m.forster@ikmb.uni-kiel.de

More information:
Institute of Clinical Molecular Biology, Kiel University 
www.ikmb.uni-kiel.de


Christian-Albrechts-Universität zu Kiel
Press, Communication and Marketing, Dr Boris Pawlowski, Text/editing: Christian Urban
Postal address: D-24098 Kiel, Germany, 
Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Jubilee: www.uni-kiel.de/cau350
Twitter: www.twitter.com/kieluni, Facebook: www.facebook.com/kieluni

Evolution of Metabolic Dependency as Base for Ancestral Symbiosis

Jun 26, 2018

Kiel research team describes the fundamental mechanisms which control the evolutionary ancient symbiotic relationship between algae and cnidarians for the first time

When life on earth developed, symbiotic associations arose as a successful strategy millions of years ago, with which organisms of different species cooperate as a close-knit community, to gain an advantage in the struggle for survival. However, we still largely do not know why they do this, what the real benefits of such partnerships are, and which molecular mechanisms are important. Scientists from the Collaborative Research Centre (CRC) 1182 “Origin and Function of Metaorganisms” at Kiel University (CAU), together with Japanese researchers from the Okinawa Institute of Science and Technology (OIST) and Okayama University, have now presented the first comprehensive characterisation of symbiotic interactions, using the example of the cooperation between the freshwater polyp Hydra and the Chlorella algae living inside its cells. Their results have been jointly published in the current issue of the internationally-renowned scientific journal eLife.

In order to investigate the fundamental mechanisms of this symbiosis, the research team focused on the metabolic relationships between Hydra and its algae symbiont. The organisms live in a so-called photosynthetic symbiosis: the algae provide their host with certain metabolic products which they obtain from the conversion of solar energy. In return, they obtain nutrients from the polyps which they cannot acquire by themselves. “This form of coexistence between cnidarians and algae is an extreme form of symbiosis, in which the algae can no longer survive without their host. The symbiotic algae even give up parts of their own genetic information, and instead use the corresponding structures of the freshwater polyps,” explained Professor Thomas Bosch, cell and developmental biologist at the CAU and spokesperson for the CRC 1182, regarding the extent of the co-dependence between the species. The Hydra are also highly dependent on their symbionts, since the Chlorella colonisation boosts their reproductive success, so the organisms’ viability would be at a considerable disadvantage without the algae.

“Our results also show which specific tools are required at a genetic and molecular level to ensure that a durable and stable symbiosis can develop in the course of evolution,” continued Bosch. On the one hand, laboratory studies revealed that the presence of the symbionts led to significant up-regulation of certain Hydra genes responsible for the metabolism, boosting the nutrient transport between host and symbiont. On the other hand, analysis of the genome of the symbiotic algae revealed that the symbiont is missing the genetic components required to utilise nitrogen, so that the nutrient supply must be partly taken over by the host.

Overall, this new publication answers one of the most important research questions in the first funding phase of the CRC 1182: the driving forces behind the evolution and long-term stability of a symbiosis. The analysis of the interactions between Hydra polyps and algae makes it clear that the co-evolution of organisms can be driven in particular by the possibility of mutual nutrient exchange. The scientists in Kiel, together with their international colleagues, now plan to build on the results of their research and investigate more complex, multi-organismic interaction networks.

A better understanding of the symbiotic relationships between cnidarians and algae is not only valuable in terms of basic scientific knowledge gained, but can also serve as a model for the assessment of climate change, associated with the change of marine ecosystems: corals, for example, are greatly threatened by the impact of global changes since their ability to absorb nutrients is dramatically affected by changes in the nutrient content of sea water. In turn, the diverse, vibrant, tropical reef-based communities depend on the health and growth of the corals. As corals – like freshwater polyps – are dependent on certain symbiotic bacteria for their nutrient uptake, a more accurate understanding of the underlying mechanisms is required. Further research is necessary to determine whether the new knowledge gained is also applicable to the symbiosis of corals and bacteria, and if this can lead to possible future adaptation strategies for protecting endangered tropical coral reefs.

Original publication:
Mayuko Hamada, Katja Schröder, Jay Bathia, Ulrich Kürn, Sebastian Fraune, Mariia Khalturina, Konstantin Khalturin, Chuya Shinzato, Nori Satoh, Thomas C G Bosch (2018): Metabolic co-dependence drives the evolutionarily ancient HydraChlorella symbiosis eLife DOI 10.7554/eLife.35122

A photo is available for download under:

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2018/207-hydra-chlorella.jpg
Caption: Microscopic view of Hydra-cells (nuclei appear in green) containing about 20-30 symbiotic Chlorella-algae each (in orange).
Image: Jay Bathia

Contact:
Prof. Thomas Bosch
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

More information:
Priority research area “Kiel Life Science”, Kiel University
www.kls.uni-kiel.de

eLife digest, eLife Sciences Publications

Kiel University
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban
Postal address: D-24098 Kiel, Germany, Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Twitter: www.twitter.com/kieluni
Facebook: www.facebook.com/kieluni, Instagram: www.instagram.com/kieluni

 

Marine fungi contain promising anti-cancer compounds

Oct 28, 2015

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A Kiel-based research team has identified fungi genes that can develop anti-cancer compounds

To date, the ocean is one of our planet's least researched habitats. Researchers suspect that the seas and oceans hold an enormous knowledge potential and are therefore searching for new substances to treat diseases here. In the EU "Marine Fungi" project, international scientists have now systematically looked for such substances specifically in fungi from the sea, with help from Kiel University and the GEOMAR Helmholtz Centre for Ocean Research Kiel. A particularly promising finding is the identification of the genes of one of these fungi, which are responsible for the formation of two anti-cancer compounds - so-called cyclic peptides. A research team headed by Professor Frank Kempken, Head of the Department of Genetics and Molecular Biology in Botany at Kiel University, has now published these new findings in the current edition of PLOS One. Read more...

Why the Japanese live longer

Nov 13, 2015

Kiel-based research team shows positive influence on life span of bioactive plant compounds in green tea and soy

A research team at the Institute of Human Nutrition and Food Science at Kiel University has discovered promising links between life expectancy and two phytochemicals - the so-called catechins and isoflavones. The underlying research by the Kiel-based scientists recently appeared in the two journals Oncotarget and The FASEB Journal. Read more...

Cellular memory outwits pathogens

Sep 13, 2018

Study by Kiel Evolution Center proves effectiveness of sequential antibiotic treatment against the pathogen Pseudomonas aeruginosa

The World Health Organization (WHO) warns that seemingly harmless bacterial infections could develop into one of the leading causes of death in the next few years, particularly in the industrialised countries. This dramatic threat arose because, in many cases, the antibiotics that have been prescribed for decades as a standard treatment have become ineffective due to increasing resistance, and this trend continues to gather pace. The root of the problem is the germs’ rapid evolutionary adaptation to the drugs used to combat them. The consequence is that even new antibiotics can become ineffective within a short period of time. Researchers around the world are therefore pursuing an alternative approach to the worsening antibiotics crisis, in order to regain the upper hand. They are trying to prolong the effectiveness of currently available active substances, through the application of evolutionary biological principles. A research team from the Kiel Evolution Center (KEC) at Kiel University (CAU) has teamed up with colleagues at the Max Planck Institute for Evolutionary Biology in Plön and Uppsala University in Sweden to reveal a previously-unknown principle, which enables a completely new and at the same time highly sustainable form of treatment. The scientists published their results yesterday in the renowned scientific journal PNAS.

The treatment process investigated makes use of a simple principle: short-term application of a particular antibiotic is followed by another antibiotic with a different mechanism of action. Using the example of the bacterium Pseudomonas aeruginosa, which according to the WHO is one of the most critical threats of a multidrug resistant bacterium, the Kiel researchers tested the temporal alternation of antibiotics with different mechanisms of action. To do so, they examined around 200 bacterial populations in an evolution experiment over a total of 500 generations, and observed the effects of different antibiotics and various sequential treatment protocols. They discovered that the most effective sequential protocol started with a penicillin-like substance followed by a so-called aminoglycoside, especially if changes happen in short intervals.

"A short initial treatment makes the germs vulnerable, because it enables easier penetration of the bacterial cells by another drug. The second antibiotic basically finishes the job, and properly kills the remaining bacteria," explained Professor Hinrich Schulenburg, head of the Evolutionary Ecology and Genetics research group at the CAU, and KEC spokesperson. This effect is entirely dependent on the sequence of the alternating antibiotics. The sensitizing drug must be applied first, since it apparently modifies the structure of the bacterial cell walls, and thereby opens the door for the second antibiotic. In addition, the speed and the pattern of the sequence are decisive: "If we alternate the two drugs faster than in normal antibiotic treatment, and at random intervals, the then resistance evolution is inhibited most effectively," continued Schulenburg.

The reason for the success of the sequential treatment is the so-called cellular memory of the bacterial pathogens. The first antibiotic changes the cellular properties of the germs over multiple generations, to such an extent that the second antibiotic functions even better - despite being administered later. "It’s almost like the first antibiotic opens a door, which provides easier entry for the second antibiotic," explained Dr Roderich Römhild, research associate in the Evolutionary Ecology and Genetics research group, and first author of the publication. "This approach is particularly promising from an evolutionary point of view, since the pathogens are now forced to evolve a defence against opening the door - and thus against the cellular memory effect - instead of direct resistance to the antibiotic," said Römhild. In the experiment, a significant reduction in resistance was indeed confirmed.

Most surprisingly, around 30 years ago, exactly the same treatment protocol as the one proposed now was by coincidence tested on patients - with impressive results: in almost all cases, pathogen abundance was significantly reduced following the sequential antibiotic treatment; in half of the cases, the pathogens could no longer be detected, and the sequential protocol was clearly more effective than the standard treatment. However, the method never became part of medical practice, most likely because of the lack of an explanation for treatment success. "We are convinced that with our new results on the cellular memory effect, we have now found the missing explanation," emphasised Schulenburg. "The new work provides yet another example of how, with the help of evolutionary concepts and methods, we can obtain new ideas for sustainable treatment approaches," summarised the KEC spokesperson.

Original publication:
Roderich Roemhild, Chaitanya S. Gokhale, Philipp Dirksen, Christopher Blake, Philipp Rosenstiel, Arne Traulsen, Dan I. Anderson, Hinrich Schulenburg (2018): Cellular hysteresis as a principle to maximize the efficacy of antibiotic therapy PNAS doi.org/10.1073/pnas.1810004115

Photos are available to download:
A short pre-treatment with penicillin increases the effectiveness of a subsequently applied aminoglycoside. Here we see a dilution series of a bacterial sample after the end of treatment, either without (3 columns on the left) or with pre-treatment (3 columns on the right).
© Christian Urban, Uni Kiel

Dr Roderich Römhild examined the effect of sequential antibiotic treatment on the pathogen Pseudomonas aeruginosa.
© Christian Urban, Uni Kiel

Antibiotic resistance remains low, thanks to the memory effect and sequential treatment. Bacteria from the evolution experiment grown on an antibiotics gradient plate, with the concentrations increasing from left to right. Pathogens from the sequential treatment are at the bottom of the image, and have not evolved an ability to cope with high antibiotic concentrations - in contrast to the control group shown above.
© Christian Urban, Uni Kiel


Contact:
Prof. Hinrich Schulenburg
Spokesperson “Kiel Evolution Center” (KEC), Kiel University
Tel.:     +49 (0)431-880-4141
E-mail:     hschulenburg@zoologie.uni-kiel.de

More information:
Evolutionary Ecology and Genetics research group, Zoological Institute, Kiel University
www.uni-kiel.de/zoologie/evoecogen

Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

Max Planck Institute for Evolutionary Biology in Plön:
www.evolbio.mpg.de


Kiel University
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban
Postal address: D-24098 Kiel, Germany,
Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Twitter: www.twitter.com/kieluni
Facebook: www.facebook.com/kieluni, Instagram: www.instagram.com/kieluni

 

New approach to antibiotic therapy is a dead end for pathogens

Jun 01, 2017

Kiel-based team of researchers uses evolutionary principles to explore sustainable antibiotic treatment strategies

The World Health Organization WHO is currently warning of an antibiotics crisis. The fear is that we are moving into a post-antibiotic era, during which simple bacterial infections would no longer be treatable. According to WHO forecasts, antibiotic-resistant pathogens could become the most frequent cause of unnatural deaths within just a few years. This dramatic threat to public health is due to the rapid evolution of resistance to antibiotics, which continues to reduce the spectrum of effective antibacterial drugs. We urgently need new treatments. In addition to developing new antibiotic drugs, a key strategy is to boost the effectiveness of existing antibiotics by new therapeutic approaches.

The Evolutionary Ecology and Genetics research group at Kiel University uses knowledge gained from evolutionary medicine to develop more efficient treatment approaches. As part of the newly-founded Kiel Evolution Center (KEC) at Kiel University, researchers under the direction of Professor Hinrich Schulenburg are investigating how alternative antibiotic treatments affect the evolutionary adaptation of pathogens. In the joint study with international colleagues now published in the scientific journal Molecular Biology and Evolution, they were able to show that in the case of the pathogen Pseudomonas aeruginosa, the evolution of resistance to certain antibiotics leads to an increased susceptibility to other drugs. This concept of so-called "collateral sensitivity" opens up new perspectives in the fight against multi-resistant pathogens.

Together with colleagues, Camilo Barbosa, a doctoral student in the Schulenburg lab, examined which antibiotics can lead to such drug sensitivities after resistance evolution. He based his work on evolution experiments with Pseudomonas aeruginosa in the laboratory. This bacterium is often multi-resistant and particularly dangerous for immunocompromised patients. In the experiment, the pathogen was exposed to ever-higher doses of eight different antibiotics, in 12-hour intervals. As a consequence, the bacterium evolved resistance to each of the drugs. In the next step, the researchers tested how the resistant pathogens responded to other antibiotics which they had not yet come into contact with. In this way, they were able to determine which resistances simultaneously resulted in a sensitivity to another drug.

The combination of antibiotics with different mechanisms of action was particularly effective - especially if aminoglycosides and penicillins were included. The study of the genetic basis of the evolved resistances showed that three specific genes of the bacterium can make them both resistant and vulnerable at the same time. "The combined or alternating application of antibiotics with reciprocal sensitivities could help to drive pathogens into an evolutionary dead end: as soon as they become resistant to one drug, they are sensitive to the other, and vice versa," said Schulenburg, to emphasize the importance of the work. Even though the results are based on laboratory experiments, there is thus hope: a targeted combination of the currently-effective antibiotics could at least give us a break in the fight against multi-resistant pathogens, continued Schulenburg.

Original publication:
Camilo Barbosa, Vincent Trebosc, Christian Kemmer, Philip Rosenstiel, Robert Beardmore, Hinrich Schulenburg and Gunther Jansen (2017): Alternative Evolutionary Paths to Bacterial Antibiotic Resistance Cause Distinct Collateral Effects. Molecular Biology and Evolution
doi.org/10.1093/molbev/msx158

Photos/material is available for download:

www.uni-kiel.de/download/pm/2017/2017-171-1.jpg
Caption: The pathogen Pseudomonas aeruginosa during the evolution experiment in the laboratory.
Image: Camilo Barbosa/Dr. Philipp Dirksen

www.uni-kiel.de/download/pm/2017/2017-171-2.jpg
Caption: Doctoral student Camilo Barbosa examined the effect of "collateral sensitivity", which can make antibiotic-resistant bacteria treatable.
Photo: Christian Urban, Kiel University

www.uni-kiel.de/download/pm/2017/2017-171-3.jpg
Caption: The research team analysed a total of 180 bacterial populations of the pathogen Pseudomonas aeruginosa.
Photo: Christian Urban, Kiel University

www.uni-kiel.de/download/pm/2017/2017-171-4.jpg
Caption: The bacteria became resistant to certain antibiotics, but at the same time sensitive to other substances.
Photo: Christian Urban, Kiel University

Contact:
Prof. Hinrich Schulenburg
Spokesperson “Kiel Evolution Center” (KEC), Kiel University
Tel.: +49 (0)431-880-4141
E-mail: hschulenburg@zoologie.uni-kiel.de

More information:
Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

Evolutionary Ecology and Genetics research group, Zoological Institute, Kiel University:
www.uni-kiel.de/zoologie/evoecogen

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski
Address: D-24098 Kiel, phone: +49 (0431) 880-2104, fax: +49 (0431) 880-1355
E-Mail: ► presse@uv.uni-kiel.de, Internet: ► www.uni-kiel.de Twitter: ► www.twitter.com/kieluni, Facebook: ► www.facebook.com/kieluni, Instagram: ► www.instagram.com/kieluni Text / Redaktion: ► Christian Urban

 

What makes the Red Queen tick?

Jan 23, 2019

Kiel Evolution Center provides new insights into the genetic basis of evolutionary dynamics
 

"Now, here, you see, it takes all the running you can do, to keep in the same place" This advice from the Red Queen in the book "Through the Looking-Glass" by the British author Lewis Carroll serves as a metaphor for a fundamental principle in the field of evolutionary biology. The "Red Queen hypothesis", named after Carroll’s figure, states that all living organisms must constantly adapt and change, in order to survive in a constantly-changing environment. This pressure to change determines the resulting evolutionary dynamics, i.e. the ongoing reciprocal adaptations of various organisms to each other and to altered environmental conditions. Although the “Red Queen hypothesis” has been explored comprehensively at the theoretical level, to date a detailed understanding of the underlying selection mechanisms and the genes involved is still missing. A research team from the Kiel Evolution Center (KEC) at Kiel University (CAU) and the Max-Planck Institute for Evolutionary Biology (MPI) together with international colleagues, has now presented an experimental analysis of these dynamics, and the genetic information which controls this process. The researchers published their results in the current issue of the journal Proceedings of the National Academy of Sciences (PNAS).

In order to experimentally investigate the underlying evolutionary processes, the Kiel researchers focused on the coevolution of the nematode (or thread worm) Caenorhabditis elegans and its bacterial pathogen Bacillus thuringiensis. The study revealed that different factors shape coevolution in the host and pathogen: in the host, the evolutionary response is driven by changes in different genome regions at different time points. In contrast, in the pathogen, adaptation is determined by frequency changes of certain mobile genetic elements, in this case certain so-called plasmids. "The genetic processes underlying rapid host-pathogen coevolution are more complicated than previously assumed, and differ significantly in host and pathogen," said Professor Hinrich Schulenburg, head of the Evolutionary Ecology and Genetics research group at the CAU, KEC spokesperson, and also fellow at the MPI. “The Red Queen thus works differently than we thought, and in particular the role of plasmids and their frequency have not been sufficiently taken into account thus far," continued Schulenburg.

These two processes of rapid evolutionary adaptation can be illustrated using the analogy of a football game: the respective genetic make-up of the host organism and pathogen may be compared with two teams, which must adapt to compete against each other. For example, if one team has a particularly strong attack, then the other team can respond by strengthening its own defence and simply sending a larger number of defense players onto the field. In a figurative sense, this is the approach used by the pathogen, which increases the number of mobile elements, and thus improves its ability to adapt. The nematode, on the other hand, figuratively speaking, exchanges its entire team. Specifically, this means that it adapts to the pathogen though changes in different genome regions at different time points.

In order to study the reciprocal adaptation of worm and bacteria in evolution experiments, the researchers repeatedly infected populations of nematodes with a specific strain of the pathogen. The research team monitored the ensuing coevolutionary changes in the two organisms, characterizing both phenotypic as well as genetic modifications. In this context, a particularly useful characteristic of the nematode Caenorhabiditis elegans is that it survives freezing, allowing direct comparison of offspring with their ancestors - great-grandchildren and great-grandparents can thus be set in direct relationship with each other. The scientists took advantage of this particular characteristic in order to compare worms at different stages of adaptation to the pathogen. In doing so, they discovered that coevolution occurs extremely fast, within a few generations. Likewise, it also became clear that the selection pressure on the pathogens led to changes in the frequency of specific plasmids; these are responsible for the production of toxins which are harmful to the host.

The Kiel researchers believe that the results of their experiments may have uncovered a universal principle underlying rapid evolution of pathogens. Such rapid adaptive responses could be facilitated through changes in the frequency of mobile genetic elements. This is likely to apply to other pathogens, too. Diverse pathogens possess plasmids that often carry the genes for so-called virulence factors, i.e. genetic information which determines the harmfulness for the host organism. "It is possible that pathogens adapt particularly quickly to their hosts, by simply adjusting the frequency of their plasmids, or other mobile elements. New mutations are then not necessary, at least initially," explained Schulenburg. "However, this aspect has not yet been well studied, even though such frequency differences might be important for the assessment of virulence, and thus potentially also for medical diagnosis of infectious disease," concludes Schulenburg.

Original publication:
Andrei Papkou, Thiago Guzella, Wentao Yang, Svenja Koepper, Barbara Pees, Rebecca Schalkowski, Mike-Christoph Barg, Philip C. Rosenstiel, Henrique Teotónio and Hinrich Schulenburg (2018): The genomic basis of Red Queen dynamics during rapid reciprocal host pathogen coevolution PNAS

doi:10.1073/pnas.1810402116

Photos are available to download:
Bildunterschrift: Der nur etwa einen Millimeter lange Fadenwurm Caenorhabiditis elegans lässt sich ohne Schaden zu nehmen einfrieren und kann nach dem Auftauen lebendig mit seinen Nachkommen verglichen werden.
© Prof. Hinrich Schulenburg

Bildunterschrift: Der Fadenwurm lebt in wechselseitiger Anpassung an Bacillus thurigiensis-Keime (rot eingefärbt), die als Schädlinge in seinem Inneren vorkommen.
© Prof. Hinrich Schulenburg

Bildunterschrift: KEC-Sprecher Professor Hinrich Schulenburg leitete die neue Studie zu den genetischen Grundlagen der Evolutionsdynamik.
© Gunnar Dethlefsen/EvoLUNG

Contact:
Prof. Hinrich Schulenburg
Spokesperson “Kiel Evolution Center” (KEC), Kiel University
Tel.:         +49 (0)431-880-4141
E-mail:     hschulenburg@zoologie.uni-kiel.de

More information:
Department of Evolutionary Ecology and Genetics, Zoological Institute, CAU Kiel:
www.uni-kiel.de/zoologie/evoecogen

Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

Fellow group Antibiotic resistance evolution, Max-Planck Institute for Evolutionary Biology, Plön: www.evolbio.mpg.de/3248501/antibioticresistance

 

 



 
 

 
 
 

 

 

 

Developmental Leaps on the Way to Becoming a Plant

Jul 10, 2017

German-Israeli research team under the leadership of Kiel University discovers evolutionary origin of redox regulation in plants

 


During the development of higher life forms over the course of millions of years, there have always been significant and comparatively sudden leaps in development. As a consequence, living organisms developed new skills and conquered additional habitats. In this process they adopted these abilities partly from their predecessor organisms: For example the plastids of the plants, the place where photosynthesis takes place, were originally autonomous unicellular living organisms. The developmental transformation of cyanobacteria into such cell organelles - the endosymbiosis, provided the plant cell with the ability to photosynthesize and thus the ability to produce energy from sunlight. Apparently, a similarly important common characteristic of plants and higher living organisms developed in a comparable manner: An international research team from the Institute of General Microbiology at Kiel University (CAU) and from the Israeli Weizmann Institute of Science has found evidence that the redox regulation in plant metabolism has its origin in two successive plastid endosymbiosis events. The results of the work funded by the Kiel Cluster of Excellence “The Future Ocean” have recently been published by the international research team in the renowned journal Nature Plants.

The development of plastids is of fundamental importance in the evolution of plants. Seen from a global perspective, plastids also boosted the so-called primary production, and thus provided oxygen and the nutritional basis for all life on Earth. To an extent, the cell paid an evolutionary price for the newly acquired advantage of energy production through photosynthesis. It had to react to the formation of highly reactive and potentially harmful byproducts, the radicals. Interestingly, cells have evolved the ability to sense the level of free radicals and use this information to regulate their metabolic activity by a unique type of control mechanism - redox regulation. Since oxygen in particular tends to develop radical molecules, the redox regulation gained its importance with the higher availability of oxygen in Earth’s past – a time period, which is associated with the fundamental developmental leap to multicellar life forms. In order to investigate the evolutionary origin of redox regulation, Dr. Christian Wöhle, research associate in the working group Genomic Microbiology at Kiel University, compared the redox regulated protein network of the diatom Phaeodactylum tricornutum to living organisms of various other phyla. As an evolutionarily quite simple life form, the diatom already has traits of more highly developed organisms; like plants it is able to carry out photosynthesis. In this manner, this model organism allows conclusions to higher developed plant and animal life forms to be drawn. 

Together with their international colleagues, the researchers from Kiel recognized that the development of the redox regulation of higher living organisms coincided with the process of a multistage plastid endosymbiosis. Comparison with the protein sequences of diverse predecessor organisms has shown that a sudden increase in the occurrence of redox regulated proteins took place in the predecessors of the diatoms, at the same time as the first plastids were taken up. The redox sensitive proteins change their biochemical characteristics if they come into contact with radicals. In this manner they allow the organism to adjust its metabolism to changing environmental conditions. “We were able to observe that the proteins, which are responsible for metabolism in the development of complex plant organisms always changed when new cell organelles were added”, emphasizes Wöhle, lead author of the study.

The mechanism by which the diatoms acquired the ability to be redox-regulated  consists in a transition of the genetic information from the subsequently acquired plastids into the genome of the receptive organism. The scientists found out that more than half of the genes involved in the redox regulation originate from unicellular organisms, in this case cyanobacteria. This observation supports the theory of the research team that the cell’s ability to conduct redox regulation developed through endosymbiotic gene transfer and thus laid the foundation for the development of higher plants. “Our results allow insight into the evolutionary adaptation of life to photosynthetic energy production and the resulting required expanded regulation mechanisms of the plant cell. They help us to better understand the reaction of different organisms to a long-term change in their living conditions,” summarizes co-author Professor Tal Dagan, head of the working group Genomic Microbiology at Kiel University and member of the “Kiel Evolution Center” (KEC). 
    
Original work:
Christian Wöhle, Tal Dagan, Giddy Landan, Assaf Vardi & Shilo Rosenwasser “Expansion of the redox-sensitive proteome coincides with the plastid endosymbiosis” Nature Plants, Published on May 15, 2017, 
doi:10.1038/nplants.2017.66

Images for download under:
www.uni-kiel.de/download/pm/2017/2017-225-1.jpg 
Caption: Phaeodactylum tricornutum cells showing fluorescent organelles: The nucleus is coloured in green, chloroplasts appear in red.
Image: Shiri Graff van Creveld, The Weizmann Institute of Science

Contact:
Prof. Tal Dagan
Genomic Microbiology 
Institute of General Microbiology, Kiel University
Telephone: 0431 880-5712
E-Mail: tdagan@ifam.uni-kiel.de

Dr. Christian Wöhle
Genomic Microbiology 
Institute of General Microbiology, Kiel University
Telephone: 0431 880-5744
E-Mail: cwoehle@ifam.uni-kiel.de

Further Information:
Genomic Microbiology (AG Dagan)
Institute of General Microbiology, Kiel University
www.mikrobio.uni-kiel.de/de/ag-dagan

Cluster of Excellence “The Future Ocean”, Kiel University:
www.futureocean.org

Research Center “Kiel Evolution Center“, Kiel University:
www.kec.uni-kiel.de

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski, Text/Editing: Christian Urban 
Postaal address: D-24098 Kiel, Telephone: (0431) 880-2104, Telefax: (0431) 880-1355
E-Mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Twitter: www.twitter.com/kieluni 
Facebook: www.facebook.com/kieluni, Instagram: www.instagram.com/kieluni

Structure of a central metabolic enzyme determined

Feb 01, 2019

Kiel research team provides key to functional understanding of the human mARC1 enzyme

One of the primary challenges for every living being is to determine the usefulness or harmfulness of ingested substances. In the case of food intake, for example, highly-specialised enzymes are used, which assist with the production of energy from chemically complex food substances. On the other hand, completely different enzymes are involved in breaking down certain non-usable or toxic foreign substances: similar to the immune system, they act as a protective barrier for the body to prevent the absorption of pollutants. In contrast with the specialised digestive enzymes, they are very non-specific, since they need to respond to a wide range of different chemical compounds in order to convert these to excreta. An example of such an enzyme in the human body is the so-called mARC1, which is involved in nitrogen conversion. A Kiel research team described it for the first time around ten years ago, and suspected that it has a special significance for physiology. Now, scientists from the Institute of Pharmacy and the Centre for Biochemistry and Molecular Biology at Kiel University (CAU) have succeeded in producing a high-resolution structural image of the mARC1 enzyme, using a special X-ray crystal structure analysis. This precise depiction of its spatial structure and the molecules contained inside provides the basis for a better functional understanding of the mARC1-controlled metabolic processes. The researchers, who are part of the CAU priority research area "Kiel Life Science" (KLS), recently published their results in the scientific journal Proceedings of the National Academy of Sciences (PNAS).

The Kiel researchers suspected that the enzyme plays a significant role in the metabolism, due to its universal occurrence: it is found not only in every human being, but also in all higher forms of life throughout the animal and plant kingdom. In nitrogen conversion, it triggers biochemical processes that essentially consist of either a reaction or the corresponding reverse reaction - depending on whether it binds or releases oxygen. With these fundamental mechanisms, it can play an important role in the control of pollutants: because nitrogen compounds in some cases produce either particularly toxic or mutagenic degradation products, the enzyme can contribute to their detoxification. At the same time, mARC1 is a special case, since it is only the fourth molybdenum-containing enzyme to be identified in the human metabolism - the xenobiotic metabolism is otherwise mainly characterised by enzymes containing iron.
 
"We have now been able to look inside the active centre of mARC1 in detail for the first time, and determine how it functions on the basis of its structure," said Professor Axel Scheidig, Director of the Centre for Biochemistry and Molecular Biology (BiMo) at the CAU. "The enzyme can be very effective in reducing pollutants which accumulate in the cell as metabolic products of nitrogen conversion," continued Scheidig. However, depending on the bonds it forms, mARC1 can also work in reverse. Then a toxic effect may occur, due to the conversion caused by the enzyme.

The key to determining the detailed structure was a so-called X-ray crystal structure analysis, which the Kiel research team carried out in cooperation with colleagues from the Deutsches Elektronen-Synchrotron (DESY) in Hamburg. It allowed the very weak signal of the atomic structure itself to be amplified by X-rays, through the interaction of numerous coherently-phased molecules. In this way, the researchers were able to make the structure of the enzyme visible, using the crystal made up of billions of individual molecules. However, for successful crystallisation, they first had to clean the protein molecules of the enzyme and link them with another protein in a lengthy optimisation process, without affecting the functioning of the enzyme while doing so. "We have worked on finding a way to visualise the enzyme structure for about ten years," emphasised Scheidig. "The highly precise depiction of the detailed structure of mARC1 which is now available opens the door to potential exploitation of its functions," he continued.

Now, in further research, the whole spectrum of metabolic processes controlled by mARC1 can be explored, including the organic and inorganic compounds produced. In addition, there is also a second, very similar enzyme, mARC2, whose previously-unknown structure can now also be investigated in detail. The goal of the future work is especially to explore the therapeutic potential of the two closely-related enzymes.
 
In addition to their importance for nitrogen metabolism, the mARC enzymes are also involved in the conversion of toxic plant substances such as alkaloids, as found in plants like the common ragwort. Here too, it is possible that the chemical reaction produces both harmless and harmful degradation products. Ultimately, the targeted use of enzymes allows the development of novel medicines: for example, the enzymes are involved in the activation of newly-developed blood thinning and anti-cancer drugs. This principle also originated from the working group of Professor Bernd Clement from the Institute of Pharmacy. For future developments, it is conceivable that with the help of mARC, the conversion and thereby the activation of an active substance may be controlled so that it already works in the digestive tract, and does not first have to be absorbed into the bloodstream. Researchers also refer to such medications with delayed activation in the body as "prodrugs". "From a pharmaceutical point of view, by applying this principle, we hope for an increased effectiveness, and potentially reduced side-effects," highlighted Clement.

The genetic profile of mARC1 plays a central role in this further research: here, the Kiel scientists were able to close a knowledge gap, as previous bioinformatic methods were only able to provide an incomplete picture. "We have also identified the genes that underlie the formation of the enzyme in humans," emphasised Clement. "On this basis, we will carry out a systematic functional analysis of the mARC1 enzyme in future, using model organisms," he continued. With the targeted switching on and off of these genes using different experimental methods, comparative statements about the mode of action of the enzyme and the physiological consequences for the organism will be possible.

Original publication:
Christian Kubitza, Florian Bittner, Carsten Ginsel, Antje Havemeyer, Bernd Clement and Axel Scheidig (2018): Crystal structure of human mARC1 reveals its
exceptional position among eukaryotic molybdenum enzymes. PNAS
DOI: 10.1073/pnas.1808576115

Contact:
Prof. Axel Scheidig
Centre for Biochemistry and Molecular Biology (BiMo), CAU Kiel
Tel.:     +49 (0)431 880-4286
E-mail:    axel.scheidig@strubio.uni-kiel.de

Prof. Bernd Clement
Institute of Pharmacy, CAU Kiel
Tel.:     +49 (0)431-880-1126
E-mail:     bclement@pharmazie.uni-kiel.de

More information:
Centre for Biochemistry and Molecular Biology (BiMo), CAU Kiel
www.bimo.uni-kiel.de/de/zentrum-fuer-biochemie-und-molekularbiologie-der-christian-albrechts-universitaet-zu-kiel

Pharmaceutical Chemistry Department, Institute of Pharmacy, CAU Kiel
www.pharmazie.uni-kiel.de/chem/home.htm

Kiel University (CAU)
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban
Postal address: D-24098 Kiel, Germany, Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Jubilee: www.uni-kiel.de/cau350
Twitter: www.twitter.com/kieluni, Facebook: www.facebook.com/kieluni

 

 

 

Moulds produce plant growth hormone

Feb 12, 2018

Kiel research team describes the auxin synthesis mechanisms in the fungus Neurospora crassa for the first time

Plants, bacteria and various fungi produce a specific group of hormones known as auxins. Together with other hormones, they cause plant cells to stretch and thus, for example, the rapid growth of young shoots. The manner in which plants produce these substances has been intensively studied for decades, and is accordingly described in great detail. In contrast, how this biosynthesis takes place in fungi has hardly been studied to date. We already know that some species of fungi which are plant pests are able to produce auxins, which trigger the growth of harmful tissue in their host plants. Now, for the first time, Professor Frank Kempken, head of the Department of Genetics and Molecular Biology at Kiel University, together with his working group, has described the mechanism by which the mould Neurospora crassa produces auxins. The Kiel researchers have also shown that fungi which are not harmful organisms are also able to make these growth hormones. Their findings have now been published in the scientific journal PLoS One.

As part of his dissertation, Puspendu Sardar, a doctoral researcher in Kempken's working group, initially compared the genetic building blocks of the fungus with those of other organisms. This enabled the identification of a number of genes occurring equally both in plants and in Neurospora crassa, which could possibly also trigger the formation of auxin in the mould. Sardar subsequently developed a bioinformatic model to theoretically predict the structure of the enzymes involved in producing auxins in the mould. "We found that the genes involved in the formation of growth hormones in plants are present in almost all fungi. Therefore, Neurospora crassa should theoretically also be able to produce auxins," explained Kempken, a member of the priority research area "Kiel Life Science" at Kiel University.

In the next step, the Kiel researchers examined whether the identified genes also have the predicted effect in living organisms. To do so, they switched off specific individual genes in genetically-modified mutants of the fungus, to determine their function experimentally. With this method, they were unable to determine an effect at first, until it became clear that the fungus has three alternative ways of producing auxins. The research team then switched off several genes in combination, in order to block the redundant mechanisms. Sure enough, the auxin concentration in these fungal mutants then dropped sharply. "The biosynthesis mechanism we have described suggests that auxin also fulfils a biological function in fungi which are not plant pests," emphasised Kempken.

However, what role the growth hormones could play remains unclear. The researchers at Kiel University have now provided an initial indication, with their discovery that auxin affects reproduction in Neurospora crassa: the experimentally-suppressed hormone production also led to a significant decrease in the sporulation (spore formation) of the fungus. In addition, it is currently being discussed whether Neurospora crassa may live in a symbiotic relationship with conifers. The Kiel research team’s findings thus form a basis for future determination of the biological function of auxin formation in fungi, and possibly also to discover related interactions of fungi and plants.

Original publication:
Puspendu Sardar & Frank Kempken (2018): Characterization of indole-2-pyruvic acid pathway-mediated biosynthesis of auxin in Neurospora crassa. PLoS One
doi.org/10.1371/journal.pone.0192293

Photos/material is available for download:

www.uni-kiel.de/download/pm/2018/2018-027-1.jpg
The structural prediction of the enzymes involved led the researchers to suspect that Neurospora crassa is able to produce auxins.
Image: Prof. Frank Kempken/ Puspendu Sardar

www.uni-kiel.de/download/pm/2018/2018-027-2.jpg
The suppression of auxin production led to a significant reduction in spore formation (see image: B./top right).
Photo: Prof. Frank Kempken / Puspendu Sardar

Contact:
Prof. Frank Kempken
Department of Genetics and Molecular Biology,
Botanical Institute and Botanical Gardens, Kiel University
Tel.: +49 (0)431-880-4274
E-mail: fkempken@bot.uni-kiel.de

More information:
Department of Genetics and Molecular Biology
Botanical Institute and Botanical Gardens, Kiel University
www.uni-kiel.de/Botanik/Kempken/fbkem.shtml

Priority research area "Kiel Life Science“, Kiel University
www.kls.uni-kiel.de

Kiel University
Press, Communication and Marketing, Dr. Boris Pawlowski
Address: D-24098 Kiel, phone: +49 (0431) 880-2104, fax: +49 (0431) 880-1355
E-Mail: ► presse@uv.uni-kiel.de, Internet: ► www.uni-kiel.de
Twitter: ► www.twitter.com/kieluni, Facebook: ► www.facebook.com/kieluni, Instagram: ► www.instagram.com/kieluni
Text / Redaktion: ► Christian Urban

 

Understanding nutrient cycling in the low-oxygen ocean

Feb 07, 2019

Joint press release by Kiel University and the GEOMAR
Helmholtz Centre for Ocean Research Kiel


Kiel research team develops basis for quantifying the nitrogen cycling in oceanic oxygen minimum zones

In the world's oceans, there are several large oxygen-depleted areas that scientists refer to as oxygen minimum zones (OMZs). These oceanic regions can encompass millions of square kilometres, and particularly occur where an intense ocean current and prevailing wind direction meet a broad coastline perpendicularly. Among other things, these flow conditions cause coastal upwelling, i.e. the upward movement of nutrient-rich deeper water. This in turn promotes the mass occurrence of oxygen-consuming microorganisms in the layers of water below the surface, which reduces the level of oxygen in the ocean. Such conditions occur, for example, in the Pacific Ocean off the west coast of South America, in line with Peru. A particularly extensive OMZ has formed here. A research team from the Collaborative Research Center 754 (SFB 754) "Climate-Biogeochemistry Interactions in the Tropical Ocean", a cooperation between Kiel University (CAU) and the GEOMAR Helmholtz Centre for Ocean Research Kiel, investigated the foraminifera, which are unicellular shell-forming microorganisms occurring throughout the ocean, in a new physiological study. Some species of foraminifera are adapted to oxygen-depleted environments as in the Peruvian OMZ. In this way, the scientists could improve our understanding of their metabolic processes, and thus extend the basis for quantifying the nitrogen cycle in the low-oxygen ocean. The researchers published their results in the journal Proceedings of the National Academy of Sciences (PNAS) yesterday.

The respiration of foraminifera
The Peruvian OMZ extends vertically from just below the water surface down to about 600 meters in depth. Depending on the depth of the water, little or no oxygen is present. These living conditions favour organisms which thrive either in the absence of oxygen or at varying levels of oxygen, such as various types of foraminifera. Depending on availability, they can "breathe" both oxygen as well as nitrate. As such, nitrate respiration goes hand in hand with the process of denitrification: this is the conversion of nitrate present in the water into molecular nitrogen in the absence of oxygen. The mass occurrence of foraminifera in the OMZ suggests that they play an important - but previously difficult to quantify - role in the nutrient cycle of these marine regions. “To better understand the role of foraminifera in the nutrient budget of the OMZ, we examined more closely the relationship between growth and denitrification rate of these organisms," explained Professor Tal Dagan from the Institute of General Microbiology at the CAU and co-author of the study.

Foraminifera prefer nitrogen to oxygen
The researchers determined the relationship between the metabolic activities of foraminifera and their size - or more precisely, the volume of their cells. In doing so they discovered that the studied OMZ foraminifera become bigger with increasing nitrate concentrations even in the absence of oxygen, and with that increasing cell volume they can also convert more nitrate. In contrast, the previous assumptions regarding the physiology of unicellular organisms with a nucleus, including foraminifera, suggested that the organisms in the OMZ should actually be smaller: with the decrease in oxygen supply, their metabolism should only be maintained with a smaller volume to surface ratio of their cells. Now, the Kiel scientists were able to resolve this contradiction: the analysed microorganisms from the OMZ do not prefer an environment with oxygen, as previously assumed. Instead, their primary metabolic pathway is nitrate respiration. "In fact, our investigations show that the foraminifera in the OMZ become bigger with increasing nitrate concentrations," said CAU marine biologist and co-author Dr Alexandra-Sophie Roy. "It seems that foraminifera do not prefer an oxygenated environment as previously assumed, or that they only switch to nitrate respiration in case of emergency. It rather seems that an environment without any oxygen is their natural preference," continued Roy.

An oxygen minimum zone in a test tube
In order to examine the metabolic pathways of the organisms, the researchers had to incubate living foraminifera in the laboratory. They obtained the organisms from sediment samples from Peruvian research area, via core sampling from the ocean floor. "Since the foraminifera in the Pacific off Peru have very specific living conditions, we had to simulate these parameters in the laboratory," said Dr Nicolaas Glock, leader of this study, from the Marine Geosystems research unit at GEOMAR, and a member of the SFB 754. "To reproduce the conditions, I worked in a cold room mimicking the ocean temperatures at 300 meters, and also precisely adjusted the salinity, nitrate and oxygen content of the experimental media”, continued Glock. He used a procedure that removes the oxygen from the seawater in a tiny glass container, a so-called cuvette, to simulate the oxygen depletion in the OMZ. He surrounded the investigated water samples containing living foraminifera with a vitamin C solution that was separated from the specimens by a thin silicon membrane. The oxygen slowly diffused through the membrane and was trapped within the Vitamin C solution. In this way, it was possible to reproduce the environmental conditions in the OMZ in the laboratory, and thereby characterise the physiological adaptations of the foraminifera to anoxia.

The influence of marine nutrient cycles on the fishing industry and climate
In the future, the theoretical basis for denitrification rates of foraminifera, described by the Kiel researchers could help to develop more accurate models of the nutrient cycles. In particular, nutrient cycling plays an important role in the oxygen minimum zones: accurate models for nutrient cycling are fundamental for our understanding of marine primary production, such as plankton growth. This in turn is the basis of the food chain in the ocean, and ultimately of all fishing yields. As such, OMZs represent only about 0.1 percent of the global ocean surface, but yield around 18 percent of global fishing. Since the OMZs may have expanded due to human influence in the last 60 years, a detailed understanding of the nutrient cycle in these regions is of particular importance. In the context of climate change, it is also becoming increasingly important to be able to quantify climate-relevant substances and their levels in the OMZs more precisely in the future. "Only with models based on realistic quantities can future predictions be made about the quantities of the important nutrient nitrate in the low-oxygen ocean, or the amount of CO2 release taking place there," said Professor Andreas Oschlies from GEOMAR, and speaker of the SFB 754. "With their newly-presented research, the scientists involved have established a very good basis for better forecasts, which now also takes into account the important role of a widespread group of organisms in the nitrogen cycle," continued Oschlies.

About the CRC 754:
The Collaborative Research Centre 754 (SFB 754) "Climate and Biogeochemical Interactions in the Tropical Ocean" was established in January 2008 as cooperation between Kiel University and the GEOMAR Helmholtz Centre for Ocean Research Kiel. The SFB 754 investigates changes in ocean oxygen content, their potential impact on oxygen minimum zones and the consequences for the global interaction of the climate and biogeochemistry of the tropical ocean. The SFB 754 is funded by the German Research Foundation (DFG) and is in its third phase (2016-2019).

Original publication:
Nicolaas Glock, Alexandra-Sophie Roy, Dennis Romero, Tanita Wein, Julia Weissenbach, Niels Peter Revsbech, Signe Høgslund, David Clemens, Stefan Sommer, Tal Dagan (2019): Metabolic preference of nitrate over oxygen as an electron acceptor in Foraminifera from the Peruvian oxygen minimum zone PNAS, Published on February 06, 2019, dx.doi.org/10.1073/pnas.1813887116

Photos are available to download:
www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-uvigerina.jpg
One of the organisms involved in the metabolic processes of the nitrogen cycle present in the oxygen minimum zone off Peru is the foraminifera species Uvigerina peregrina.
© Dr Nicolaas Glock

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-labor.jpg
Lead author Dr Nicolaas Glock from the SFB 754 conducting measurements in the laboratory of the research vessel Meteor in the South American research area.
© Prof. Tal Dagan

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-autorinnen.jpg
The scientists involved in the publication, Tanita Wein, Dr Alexandra-Sophie Roy and Dr Julia Weißenbach (from left to right) sample sediment obtained from the ocean floor off the Peruvian coast.
© Prof. Tal Dagan

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-bohrkern.jpg
The researchers obtained the foraminifera investigated from such polycarbonate core tubes taken from the Pacific seabed at a depth of approximately 500 meters.
© Prof. Tal Dagan

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-foraminiferen.jpg
Some specimens of the studied species Uvigerina striata sieved out of the sediment using sieves of various sizes.
© Prof. Tal Dagan

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/33-glock-pnas-kuevettte.JPG
The researchers studied the physiology of the foraminifera in cuvettes, in which a tiny sensor measures the oxygen concentration of the water inside, among other factors.
© Prof. Tal Dagan

Contact:
Nicolaas Glock
Marine Biogeochemistry
GEOMAR Helmholtz Centre for Ocean Research Kiel
Tel.: +49 (0)431 600-2105
E-mail: nglock@geomar.de

Prof. Tal Dagan
Genomic Microbiology,
Institute of General Microbiology, Kiel University
Tel.: +49 (0)431 880-5712
E-mail: tdagan@ifam.uni-kiel.de

More information:
Collaborative Research Center (SFB) 754 "Climate-Biogeochemistry Interactions in the Tropical Ocean":
www.sfb754.de

Genomic Microbiology (Dagan working group),
Institute of General Microbiology, Kiel University:
www.mikrobio.uni-kiel.de/de/ag-dagan

Marine Geosystems research unit, GEOMAR Helmholtz Centre for Ocean Research Kiel:
www.geomar.de/forschen/fb2/fb2-mg/ueberblick/

 

Selfish chromosomes make harmful fungus vulnerable to attack

Feb 12, 2019

Members of Kiel Evolution Center discover fundamentally new traits in the inheritance mechanisms of a plant-damaging fungus

Wheat is the world's second most extensively cultivated cereal crop, and in many countries an indispensable ingredient of essential staple foods. In Germany alone, 20-25 million tons of this grain are harvested per year. However, wheat cultivation in north-western Europe faces a fungal pest, which in extreme cases can cause losses of around 50 percent of the harvest: the fight against the fungus Zymoseptoria tritici is therefore of fundamental importance for food security. Disease management has so far mainly occurred in the conventional way through the widespread use of fungicides - with all the associated disadvantages for the environment and consumers. Because the fungus is becoming more resistant to fungicides and, conversely, there are no wheat varieties that are completely resistant to the pest, scientists at Kiel University (CAU) together with colleagues worldwide are intensively researching sustainable ways to keep the fungus in check.

Translational Evolutionary Research
At the CAU, the Kiel Evolution Center (KEC) in particular is working on applying evolutionary biological principles and making them usable, among other things, for pest control. An important step in this direction has now been taken by a KEC research team, together with the Max Planck Institute for Evolutionary Biology in Plön (MPI-EB), through their investigation of the basics of inheritance in this harmful fungus, and thereby also potential ways to combat it. The Kiel researchers discovered that the so-called meiosis, i.e. the maturation division of germ cells and the associated multiplication of genetic information, occurs differently in Zymoseptoria tritici than previously thought. This fungus has additional, unpaired chromosomes that can pass on genetic information to all their offspring and not just half of the following generations. "We have found that the chromosomes, but not the fungus as a whole, gain an evolutionary advantage through this type of inheritance," emphasised Dr Michael Habig, first author of the study and research associate in the Environmental Genomics group at the CAU Botanical Institute. "Only the chromosomes themselves benefit by passing on their characteristics to all descendants, and thus in a figurative sense they act egoistically," continued Habig. The researchers described this phenomenon in Zymoseptoria tritici for the first time, and recently published their results in the journal eLife.

Meiosis - an old acquaintance from biology class?
At the centre of the newly-described inheritance process is meiosis, which is a key step in sexual reproduction, and apparently takes place fundamentally differently in this fungus than previously thought. In normal so-called Mendelian inheritance, it serves to combine the different maternal and paternal chromosomes in the form of so-called homologous chromosomes, and pass these on to the descendants. In this way, the offspring inherit half of their genetic characteristics from both the mother and father. In contrast, meiosis seems to take place differently in Zymoseptoria tritici - especially regarding the so-called supernumerary chromosomes, which cannot combine with the relevant paternal or maternal counterpart. These unpaired chromosomes are thus inherited exclusively from either the mother or the father. The researchers were able to demonstrate that the maternal supernumerary chromosomes are passed on to all descendants, and not as expected only half of the descendants. "The driving force behind this strategy is the so-called meiotic drive, which ensures the increased transmission of chromosomes to the next generation," emphasised Professor Eva Stukenbrock, head of the Environmental Genomics group, which is jointly based at the CAU and the MPI-EB, and board member of the KEC. "This alternative method of inheritance was already known from other organisms. We could now prove it in Zymoseptoria tritici, and have found very many of the chromosomes involved in this meiotic drive," continued Stukenbrock.

A potential gateway to combating wheat pests
For the organism as a whole, inheritance through supernumerary chromosomes seems to be mainly a negative process. Why the fungus has nevertheless retained this in the course of evolution, over a long period of time, has not yet been fully understood. On the one hand, it inhibits the fungus’ ability to infect wheat, but on the other hand possibly increases its ability to adapt to changing environmental conditions. However, the Kiel researchers particularly see the chromosomes’ egotistical strategy as offering potential for new means of combating the harmful fungus in future. "Perhaps we will be able to introduce specific genetic information into the fungus through this special type of inheritance, which could substantially reduce its harmfulness to wheat," Habig said optimistically. "In doing so, one could take advantage of the fact that all offspring will be equipped with the corresponding genetic information," added Habig. The methods required to do this, such as so-called genome editing, are currently being intensively researched worldwide. So in future, the principle discovered at the KEC could help to permanently protect wheat plants against attack by Zymoseptoria tritici.

Original publication:
Michael Habig, Gert HJ Kema and Eva Holtgrewe Stukenbrock (2018):
Meiotic drive of female-inherited supernumerary chromosomes in a pathogenic fungus eLife
DOI: 10.7554/eLife.40251.001

Photos are available to download:
www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/039-habig-elife-blatt.jpg
A wheat leaf infested with the fungus Zymoseptoria tritici shows the typical signs of so-called leaf blotch, which can lead to drastic crop failures.
© Dr Janine Haueisen

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/039-habig-elife-infekt.jpg
Confocal microscope image of the infection of a wheat plant: the fungus penetrates the stomata of the leaves, and can spread between the plant cells.
 © Dr Janine Haueisen

Contact:
Dr Michael Habig
Environmental Genomics group
Botanical Institute, Kiel University
Tel.:     +49 (0)431-880 -6361
E-mail:     mhabig@bot.uni-kiel.de

Prof. Eva Stukenbrock
Head of the Environmental Genomics group
Botanical Institute, Kiel University
Tel.:     +49 (0)431-880 -6368
E-mail:     estukenbrock@bot.uni-kiel.de

More information:
Environmental Genomics group, Botanical Institute, Kiel University/
Max Planck Institute for Evolutionary Biology in Plön:
http://web.evolbio.mpg.de/envgen/

Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

 

 

Conquering the Extreme

Credit: ESO/G. Beccari, License: CC BY 4.0, http://www.eso.org/public/images/eso1723a/

May 04, 2018

How microorganisms support multicellular organisms with the colonisation of hostile environments

From hot and nutrient-poor deserts to alternating dry and wet intertidal zones, right through to the highest water pressure and permanent darkness in the deep sea: in the course of its development over millions of years, life has conquered even the most extreme places on earth. That termites can live off indigestible wood, plants can exist in deserts - seemingly without water and nutrients, or sea anemones can tolerate the constant change between underwater and dry environments in intertidal zones, apparently also depends on close cooperation with their bacterial symbionts. Life scientists around the world are currently investigating the manner in which the symbiotic interaction of microorganisms and hosts, in the functional unit of a metaorganism, supports the colonisation of such extreme habitats. An international research team under the leadership of the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms” at Kiel University has now presented an inventory of mechanisms, with which the interactions of hosts and symbionts support life under extreme environmental conditions, or even make it possible at all. Together with colleagues from Saudi Arabia’s King Abdullah University of Science and Technology (KAUST), the researchers have now described in detail for the first time in the scientific journal Zoology how microorganisms can promote the growth and the evolutionary fitness of different organisms in extreme locations.

An important factor in response to changing living conditions is time. If the environment at a particular place changes very quickly, for example through drastic change in physical and chemical conditions such as light or oxygen levels, the more highly-developed multicellular organisms in particular find the adjustment difficult. Their ability to adapt is too slow, because the required genetic change can only be completed over the course of several generations. "Here microorganisms can give their host organisms an advantage," emphasised Professor Thomas Bosch, cell and developmental biologist at Kiel University and spokesperson for the CRC 1182. "With bacteria, for example, the evolutionary processes occur much more rapidly. They can partially transfer this ability to respond much faster to environmental changes to their hosts, and thereby assist the hosts with adaptation," continued Bosch. 

The lack of food or the inability to actually use the available nutrients further limits the available habitats. The metabolisms of many organisms are geared to specific optimal living conditions, and struggle to cope in extreme areas. Here too, it is often the symbiotic relationships with bacteria which enable plants and animals to expand the functioning of their own metabolisms. Thus, different organisms can, for example, exchange nutrients with their bacterial partners, and thereby utilise food sources which their metabolisms otherwise could not process. 

Certain symbiotic bacteria, which colonise the roots of plants, help them to absorb elements such as nitrogen and other minerals in dry and nutrient-poor locations. Other bacteria support plant growth by increasing tolerance to saline soil. In the future, researchers will focus on investigating such helpful bacterial cultures, regarding their applicability to crops. Potentially, a better understanding of plants as metaorganisms could also help to utilise previously-unusable deserts for agriculture in the future.

In addition, microbial symbionts enable various organisms to develop a high tolerance towards a rapidly-changing environment: fixed cnidarians in the inter-tidal zones of different oceans can, for example, quickly adapt to the extreme changes in their living conditions because they can also abruptly change the composition of their bacterial colonisation. Behind this lie mechanisms such as the direct exchange of genetic information between different bacterial species, which controls the exclusion or inclusion of specific types of bacteria in the metaorganism. "In sea anemones, their bacterial colonisation changes in accordance with the prevailing site conditions," emphasised Dr Sebastian Fraune, research associate at the Zoological Institute at Kiel University. "The organisms can potentially save this flexible bacterial configuration, and recall it in the event of a change in their habitat, in order to cope with the new conditions," continued Fraune.

From the investigation of this bacterial-controlled ability to adapt to fast-changing environmental conditions, it may be possible in future to draw conclusions about the effects of climate change on organisms and ecosystems, or even to deduce adaptation strategies. Further research will clarify how the health and fitness of a metaorganism depend on the adaptability of its individual partners, and what effects arise from changing individual elements of this complex structure. The new findings thus emphasise the fundamental importance of researching the multi-organismic relationships between hosts and microorganisms, in particular, too, for the understanding of life in a variable and extreme environment.


Original publication:
Corinna Bang, Tal Dagan, Peter Deines, Nicole Dubilier, Wolfgang J. Duschl, Sebastian Fraune, Ute Hentschel, Heribert Hirt, Nils Hülter, Tim Lachnit, Devani Picazo, Lucia Pita, Claudia Pogoreutz, Nils Rädecker, Maged M. Saad, Ruth A. Schmitz, Hinrich Schulenburg, Christian R. Voolstra, Nancy Weiland-Bräuer, Maren Ziegler, Thomas C.G. Bosch (2018): Metaorganisms in extreme environments: do microbes play a role in organismal adaptation? Biology doi.org/10.1016/j.zool.2018.02.004


A photo is available for download under:
www.uni-kiel.de/download/pm/2018/2018-131-1.jpg 
Associated microbiota can promote the host’s vigour and proliferation in extreme environments. Such insights may be informative even when attempting to remotely detect the presence of life in extreme conditions on terrestrial planets. The Photograph shows the spectacular Orion Nebula, 
taken by ESO’s VLT Survey Telescope (VST).
Credit: ESO/G. Beccari, License: CC BY 4.0, http://www.eso.org/public/images/eso1723a/ 

Contact:
Prof. Thomas Bosch
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

More information:
Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

KAUST news release on the related „Metaorganism Frontier Research Workshop“:
www.kaust.edu.sa/en/news/exploring-the-metaorganism-frontier


Christian-Albrechts-Universität zu Kiel
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban 
Postal address: D-24098 Kiel, Germany, Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Twitter: www.twitter.com/kieluni 
Facebook: www.facebook.com/kieluni, Instagram: www.instagram.com/kieluni

 

What the metabolism reveals about the origin of life

May 07, 2018

Kiel botanist proposes new theory for the simultaneous evolution of opposing metabolic processes

Which came first, the chicken or the egg? This classical ‘chicken-or-egg’ dilemma applies in particular to the developmental processes of life on earth. The basis of evolution was a gradual transition from purely chemical reactions towards the ability of the first life forms to convert carbon via metabolic processes, with the help of enzymes. In this transition, early life forms soon developed different strategies for energy production and matter conversion. 

In principle, science distinguishes between so-called heterotrophic and autotrophic organisms: the first group, which includes all animals for example, uses various organic substances as energy sources. Their metabolic processes produce CO2 - amongst other things - during respiration. In contrast, autotrophic organisms exclusively use inorganic carbon compounds for their metabolism. This group includes all plants, which carry out photosynthesis and thereby bind CO2 to gain energy from sunlight.

In evolution research, scientists around the world have long discussed which of the two basic metabolic strategies developed first - autotrophy or heterotrophy, i.e. photosynthesis or respiration. Dr Kirstin Gutekunst, research associate in the Plant Cell Physiology and Biotechnology Group at the Botanical Institute at Kiel University, proposes instead that both developments may have occurred simultaneously and in parallel. The Kiel botanist presents this novel theory for discussion, which she has titled "Hypothesis on the Synchronistic Evolution of Autotrophy and Heterotrophy", in the journal Trends in Biochemical Sciences.

Gutekunst argues as follows: in terms of matter conversion, the earth represents a closed system. The quantity of every kind of matter on earth cannot be changed - it is only continuously converted and reassembled. There must therefore be a balance in such a system - otherwise certain substances would be permanently removed and others permanently added. The logical conclusion is that for every metabolic process, there must be a corresponding opposing process - either within the same organism, or in two different organisms which have opposing metabolic processes. A third core argument of the new hypothesis lies in the fact that the main drivers of the metabolism, the enzymes, can inherently act in two directions - so therefore, every metabolic reaction can be reversed by the corresponding opposing reaction. Metabolic processes overall are not linear, but rather cyclical, and have a global balance of materials.

"The current scientific knowledge suggests that heterotrophy and autotrophy cannot have developed independently of each other. In a closed system that is characterised by a balance of materials, then both metabolic processes are interdependent," said Kirstin Gutekunst. "Just like neither the chicken nor the egg could have originated first, so too heterotrophic and autotrophic organisms cannot have developed after each other," continued the Kiel plant researcher. An example of this kind of balance of materials can be found in cyanobacteria, also known as blue-green algae. They combine the metabolic processes of photosynthesis and respiration in one organism, and thus display heterotrophic and autotrophic properties at the same time. Here, these processes are particularly closely linked, and are based on identical molecular components.

The new theory of the Kiel researcher could thus provide impetus to re-evaluating the existing conception of the origin of life on earth in future. In principle, the question of origin can only be viewed hypothetically. However, Gutekunst’s theory offers credible indices against the idea of a singular origin, which in essence is technically based on an unscientific idea of creation. In contrast, the proposed synchronistic hypothesis suggests a duality right from the beginning of evolution. If metabolic processes based on the effect of enzymes are acknowledged as a characteristic of life, then for each reaction there must also be an opposing reaction. Such an evolution can therefore only have started at the same time, and from there onwards developed in parallel. Gutekunst’s thesis is thus a strong argument against the assumption of a singular origin of autotrophy or heterotrophy.

The publication forms part of the plant research conducted within the priority research area "Kiel Life Science" at Kiel University. Currently, the scientists in this area are striving to network with each other better, and to encourage mutual exchange of ideas and information. In this context, together with partner institutions in the region, they are preparing the formation of an independent, interdisciplinary centre for plant research at Kiel University.

Original publication:
Kirstin Gutekunst (2018): Hypothesis on the Synchronistic Evolution of Autotrophy and Heterotrophy Trends in Biochemical Sciences
doi.org/10.1016/j.tibs.2018.03.008

Photos are available to download:
www.uni-kiel.de/download/pm/2018/2018-134-1.jpg 
Caption: The Hypothesis on the Synchronistic Evolution of Autotrophy and Heterotrophy assumes that the opposing processes must have developed at the same time.    
Image: Dr Kirstin Gutekunst

Contact:
Dr Kirstin Gutekunst
Plant Cell Physiology and Biotechnology Group,
Botanical Institute and Botanical Gardens, Kiel University
Tel.:         +49 (0)431-880-4237
E-mail:     kgutekunst@bot.uni-kiel.de

More information:
Plant Cell Physiology and Biotechnology Group,
Botanical Institute and Botanical Gardens, Kiel University
www.biotechnologie.uni-kiel.de

Priority research area “Kiel Life Science”, Kiel University
www.kls.uni-kiel.de

Christian-Albrechts-Universität zu Kiel
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban
Postal address: D-24098 Kiel, Germany, Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de
Twitter: www.twitter.com/kieluni, Facebook: www.facebook.com/kieluni

 

Intestinal microbiota defend the host against pathogens

Mar 01, 2019

Research team from the Kiel CRC 1182 examines the role of the intestinal microbiome in fighting infections, using the nematode model Caenorhabditis elegans

From single-celled organisms to humans, all animals and plants are colonised by microorganisms. As so-called host organisms, they accommodate a diverse community of symbiotic microorganisms, the microbiome, and together with them form the so-called metaorganism. The interactions between host and microbes exert a significant influence on diverse functions and health of the host organism. Scientists from the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms” at Kiel University (CAU) are investigating these complex interactions, and attribute an important role in the defence against pathogens to the microbiota. To do so, they use various experimental model organisms, i.e. living organisms which allow investigation of the interaction with their bacterial symbionts under laboratory conditions. A research team from the department of Evolutionary Ecology and Genetics at CAU has examined the function of the natural intestinal microbiome using the nematode (round worm) model Caenorhabditis elegans. They discovered that the natural C. elegans microbiome plays an important role in the defence against infections, and that certain bacteria produce a compound with a clear antimicrobial effect. In future, the results of the Kiel scientists could help to better understand the functions of the intestinal microbiome as a whole, and in particular its effects on the colonisation of the digestive tract by pathogens. Their study was published today in the scientific journal Current Biology.

Direct and indirect protection against infection
The Kiel team laid the foundation for the current research results a few years ago, when it presented the first systematic analysis of the natural worm microbiome. This investigation led to a detailed knowledge of the composition and the dominant species of the intestinal microbiome of the worm. At that time, the researchers hypothesised that the natural microbiome benefits host fitness, for example by protecting the host against pathogens. To gain a better understanding of the function of the worm microbiome, the researchers have now examined how individual bacteria from the former study affect the fitness of the host during pathogen infection. In doing so, they identified two distinct modes of action.

"On the one hand, we were able to determine a direct protective effect of certain bacteria against a pathogen," said Dr Katja Dierking, research associate in the department of Evolutionary Ecology and Genetics at CAU, and principle investigator in the CRC 1182. "Microbiota bacteria of the genus Pseudomonas inhibit the growth of the nematode specific pathogen Bacillus thuringiensis, if you put them in direct contact with each other," continued Dierking. In addition, the study of other microbiota bacteria of the genus Pseudomonas revealed an indirect effect: although they do not inhibit the growth of the pathogen directly, they nevertheless protect the worm against its harmful effects, likely through indirect, host-mediated mechanisms. The researchers found a total of six bacterial isolates in the natural microbiome which are involved in the defence against infections: two of them protect the worm directly against pathogens, and four of them indirectly.

How intestinal bacteria inhibit the growth of pathogens
Another special feature of the new Kiel study is that it not only describes the infection-inhibiting effect of individual bacteria of the worm’s microbiome, but was also able to identify an underlying molecular mechanism. Using genomic and biochemical analyses, the scientists from the Kiel CRC 1182 in collaboration with scientists from Goethe University Frankfurt were able to identify an antibacterial compound that is produced by the two Pseudomonas microbiota bacteria, which protect the worm by directly inhibiting pathogen growth. "The Pseudomonas bacteria produce a so-called cyclic lipopeptide," explained Kohar Kissoyan, first author of the study and doctoral researcher in the Evolutionary Ecology and Genetics group. "This chemical compound exerts a direct inhibitory effect on the pathogen, and thereby suppresses its further growth," continued Kissoyan.

How can we utilise the new findings?
The new results of the Kiel team establish C. elegans, which is a standard model organism studied in numerous research laboratories throughout the world, as experimental system to explore the various functions of the natural intestinal microbiome. Next, Dierking and her research team want to conduct a detailed investigation of the mechanism of action of the antibacterial compound identified in the worm’s intestinal microbiome. The goal of the CRC 1182 is to understand the interactions of the various bacteria of the microbiome with the host organism, but also with each other. In the long-term, the Kiel researchers hope that the gained knowledge will help in the development of therapeutic strategies to treat diseases related to disturbances of the intestinal microbiome, e.g. through the targeted use of probiotics, i.e. specific beneficial bacterial cultures. Currently, the Kiel metaorganisms CRC, which started in 2016, is applying for a second funding period as of 2020 at the German Research Foundation (DFG).

Original publication:
Kohar Kissoyan, Moritz Drechsler, Eva-Lena Stange, Johannes Zimmermann, Christoph Kaleta, Helge Bode and Katja Dierking (2019): Natural C. elegans microbiota protects against infection via production of a cyclic lipopeptide of the viscosin group Current Biology Published on February 28, 2019
DOI: 10.1016/j.cub.2019.01.050

Photos are available to download:
www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/058-dierking-currbio-platte.jpg
An agar plate demonstrates the inhibitory effect of Pseudomonas bacteria: The pathogen Bacillus thurigiensis cannot thrive next to them.
© Dr Sabrina Köhler

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/058-dierking-currbio-lab.jpg
Dr Katja Dierking (in the background) and Kohar Kissoyan investigated the role of C. elegans’ natural microbiome in the defence against infections.
© Dr Sabrina Köhler

Contact:
Dr Katja Dierking
Evolutionary Ecology and Genetics group, Kiel University
Tel.:     +49 (0)431-880-4145
E-mail:     kdierking@zoologie.uni-kiel.de

More information:
Department of Evolutionary Ecology and Genetics, Zoological Institute, Kiel University:
www.uni-kiel.de/zoologie/evoecogen

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Kiel University (CAU)
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban
Postal address: D-24098 Kiel, Germany, Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355 E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Twitter: www.twitter.com/kieluni
Facebook: www.facebook.com/kieluni, Instagram: www.instagram.com/kieluni

 

Over-fed bacteria make people sick

May 15, 2019

In a new hypothesis, a CRC 1182 research team suggests that inflammatory diseases are caused by an over-supply of food, and the associated disturbance of the intestine’s natural bacterial colonisation.  

Since the end of the Second World War, along with the growing prosperity and the associated changes in lifestyle, numerous new and civilisation-related disease patterns have developed in today's industrialised nations. Examples of the so-called "environmental diseases" are different bowel inflammations like Crohn's disease or ulcerative colitis. Common causes include disruptions to the human microbiome, i.e. the natural microbial colonisation of the body, and in particular of the intestine. To date, scientists have explained this disrupted cooperation between host body and microbes with different hypotheses: for example, they postulated that excessive hygiene, the intensive use of antibiotics, or certain genetic factors permanently disrupt the microbiome, thus making people vulnerable to illnesses. However, these explanation attempts have so far been incomplete. A team from the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms” at Kiel University (CAU) has now formulated a new and more comprehensive ecological-evolutionary theory on the development of environmental diseases. The Kiel researchers suggest that an unnatural and particularly comprehensive nutrient supply decouples bacteria from their host organisms, and thus destroys the delicate balance of the microbiome. The, to some extent, over-fed bacteria in the gut thus promote disease development. The Kiel scientists published this fundamental new approach towards a more complete explanation of environmental diseases yesterday in the journal mBio.


The origin lies in the oceans

The starting point for the Kiel research team was the ecology of marine habitats: research on coral and algae dying off, and the associated effects on important ecosystems in the oceans, suggests that in addition to other factors such as climate change or overfishing, the nutrient conditions in the seawater may be the cause of the problem. As soon as there is an oversupply of food due to human influences, bacteria living in a community with corals begin to decouple from their hosts. They then no longer feed off the metabolic products of the host, but prefer the richer nutrient supply of the surrounding waters. The balance of the coral microbiome is disrupted because of the exodus of its symbiotic partner, and diseases occur as a result. "In this connection between nutrient availability and the balance of bacteria-host relationships, we see a universal principle which goes way beyond the very specific example of corals," explained Dr Tim Lachnit, research associate at the CRC 1182 and first author of the study. "In studies of our model organism, the freshwater polyp Hydra, we were able to experimentally confirm this connection," continued Lachnit. These small cnidarians also showed clear signs of disease as soon as their normal nutrient uptake was disturbed and an over-supply of food was available instead.

What do corals and cnidarians have to do with people?

With a high degree of probability, the knowledge gained in the experiment can also be transferred to human health. Similar to in seawater, or in the simple body cavity of a freshwater polyp, which during the course of evolution has decoupled from its external environment and a direct food supply, the nutrient supply in the human gut is also changing along with the civilisation-induced changes in eating habits - towards an unbalanced, energy-rich and low-fibre diet. In addition to direct negative health consequences, a permanently high, easy to process supply of nutrients not only affects the human metabolism it feeds, but also the bacterial colonisation of the intestine, which is also "fed". The microbes switch from the metabolites of the host as their staple food to the abundantly available nutrients from the human food and thus decouple from their interactions with the host organism. "This over-feeding of the bacteria promotes their growth as a whole, and certain species of bacteria proliferate to the detriment of other members of the microbiome in an increased and uncontrolled manner," emphasised Professor Thomas Bosch, spokesperson of the CRC 1182. "Thus, along with the change in the composition of the bacterial colonisation, the interactions between bacteria and host organism also change, and a serious maladaptation - known as dysbiosis - occurs," explained Dr Peter Deines, research associate at the Kiel metaorganism CRC.

Other civilisation-related factors increase this imbalance of the microbiome. The elimination of periodic fasting resulting from food sources not always being available, the only very rare occurrence of diarrhoea leading to episodic reductions of the intestinal bacterial colonisers and the diet-related impoverishment of the microbial diversity in the gut are just a few examples. The first two of these represent very fundamental mechanisms, which since the early development of mankind right up to the pre-industrial era enabled the microbiome to return to a normal state at regular intervals, and thus regain a healthy and natural composition.

Does the microbiome heal itself?

The "over-feeding hypothesis" proposed by researchers from the Kiel CRC 1182, in close cooperation with the CAU Cluster of Excellence "Precision Medicine in Chronic Inflammation", offers valuable approaches for further research, right through to potential transfer to future treatments: to date, scientists were particularly looking for ways to correct a disturbed microbiome through external interventions such as probiotics, i.e. the addition of certain types of helpful bacteria, or even faecal transplants to restore the balance. Now, the ecological-evolutionary perspective has added another dimension. More than ever before, it incorporates the natural ability of the microbiome to readjust itself, and to restore a healthy composition. Therefore, future research approaches lie in the specific mechanisms that balance the microbiome, and the question of whether the "overfeeding" of the bacteria can be reduced by changed eating habits. "An interesting question will be whether the original evolutionary processes which ensure the balance of the microbiome also have therapeutic potential," said Lachnit. "In the future we will, for example, not only consider the known health benefits of fasting, but also its effects on the composition and function of the microbiome, and thus on the development of inflammatory diseases," continued Lachnit.

Original publication:
Tim Lachnit, Thomas CG Bosch & Peter Deines (2019): Exposure of the host-associated microbiome to nutrient-rich conditions may lead to dysbiosis and disease development – an evolutionary perspective. mBio Published on May 14, 2019
DOI: 10.1128/mBio.00355-19

Photos are available for download under:
Caption: The fresh water polyp Hydra as a model system shows possible links between overfed microbes and the development of disease.
© Kiel Life Science

Caption: CRC 1182 researchers Dr Tim Lachnit (left) und Dr Peter Deines investigated the connections between nutrient availability and the balance of the microbiome.
© Christian Urban, Kiel University

Contact:
Dr Tim Lachnit
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4171
E-mail: tlachnit@zoologie.uni-kiel.de

Prof. Thomas Bosch
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

Dr Peter Deines
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4171
E-mail: pdeines@zoologie.uni-kiel.de

Press contact:
Christian Urban
Science communication “Kiel Life Science”   
Tel.: +49 (0)431-880-1974
E-mail: curban@uv.uni-kiel.de

More information:
AG Bosch, Kiel University:
www.bosch.zoologie.uni-kiel.de/

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com


 

 

Cancer diagnosis: no more needles?

May 25, 2018

Kiel University research team proposes extracting genetic material for research and diagnostic purposes from urine in future

Urine is an everyday liquid which most people pay little attention to and regard as rather unpleasant. It’s quite the opposite for a group of clinical researchers from Kiel University, the University Medical Center Schleswig-Holstein (UKSH) and the Lithuanian University of Health Sciences in Kaunas, who are convinced of the diagnostic potential of this yellowish liquid. The reason for this is the genetic material that urine contains – especially the so-called cell-free DNA - which offers new opportunities for cancer diagnostics. The researchers in the lab were able to extract just as much as cell-free DNA from 60 ml of urine (about half a urine beaker) as from a 10 ml blood sample. The research team is working on developing new procedures to extract cell-free DNA from urine for this purpose. Together with their international colleagues, the researchers from the Institute of Clinical Molecular Biology (IKMB) at Kiel University have now published their findings today in the current issue of the journal BioTechniques.

The term cell-free DNA refers to fragments of genetic information that are found outside of cells in various bodily fluids. These DNA components originate when body cells die - but also when tumour cells die. They are initially released into the bloodstream, and from there also make their way into the urine. The research team initially encountered a series of problems: the amount of DNA in urine differs greatly from person to person, and even varies significantly in the same person from day to day. This meant that the DNA concentrations in the samples were initially sometimes too low, so that the researchers had to increase the respective quantities of urine collected. They also regularly observed that the urine of healthy women contains more than twice as much cell-free DNA than the identical amount of urine in healthy men. This factor must be taken into account in future cancer diagnostics, so that these gender-specific differences do not distort the results. 

To date, tests for diagnosing cancer are mostly based on blood samples. Some of these blood tests use cell-free DNA, which may originate from a possible tumour, to identify certain types of lung and colon cancer. In the next twelve months, the scientists plan to carry out further research in the IKMB laboratory at Kiel University, to determine whether genetic material from urine is as suitable for clinical research and diagnostics as blood.  "To do so, we will examine available samples from study participants at the University Medical Centre, and compare the genetic traces of a tumour in the blood plasma and urine to determine whether both methods can reliably detect the disease," said Michael Forster, a scientist at the Institute of Clinical Molecular Biology at Kiel University.

In future, the researchers in Kiel hope to develop a urine-based test which is as reliable as traditional blood tests. This would primarily benefit patients, who would be spared the unpleasant blood withdrawal. In addition, such a test procedure would be faster and less expensive than the previous methods - for example, unlike with blood tests, no medical personnel are required when taking urine samples. "In the United States, a similar test procedure is already commercially available for cancer research. Recently, an international research team also presented a new urine test, which has not yet been clinically approved, for certain tumours in the urinary tract," said Forster regarding the current state of progress. "The introduction of new urine-based clinical tests in Germany still requires several years of clinical research, as well as further cost/benefit analysis," continued the molecular geneticist.

The follow-up research will be carried out in cooperation with external clinical research groups, within the framework of the new Competence Centre for Genome Analysis Kiel (CCGA Kiel). The CCGA Kiel is Germany's largest academic high-throughput sequencing centre. It has received funding from the German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF). Operating one of the four newly-created sequencing super-centres in Germany, Kiel University is servicing the exploding demand for complex genome analysis in the life sciences,.

Original publication:
Greta Streleckiene, Hayley M Reid, Norbert Arnold, Dirk Bauerschlag, Michael Forster (2018): Quantifying cell free DNA in urine: comparison between commercial kits, impact of gender and inter-individual variation BioTechniques DOI: 10.2144/btn-2018-0003

Photos are available to download:
www.uni-kiel.de/download/pm/2018/2018-165-1.jpg
The Kiel University research team would like to use urine instead of blood in future for cancer diagnosis. 
Photo: Christian Urban, Kiel University

www.uni-kiel.de/download/pm/2018/2018-165-1.jpg
The leader of the study, Michael Forster, together with his colleagues Regina Fredrik (left) and Nicole Braun from the Institute of Clinical Molecular Biology at Kiel University.
Photo: Christian Urban, Kiel University

Contact:
Michael Forster
Institute of Clinical Molecular Biology, Kiel University 
Tel.: +49 (0)431-500-15136
E-mail: m.forster@ikmb.uni-kiel.de

More information:
Institute of Clinical Molecular Biology, Kiel University 
www.ikmb.uni-kiel.de


Christian-Albrechts-Universität zu Kiel
Press, Communication and Marketing, Dr Boris Pawlowski, Text/editing: Christian Urban
Postal address: D-24098 Kiel, Germany, 
Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Jubilee: www.uni-kiel.de/cau350
Twitter: www.twitter.com/kieluni, Facebook: www.facebook.com/kieluni

Evolution of Metabolic Dependency as Base for Ancestral Symbiosis

Jun 26, 2018

Kiel research team describes the fundamental mechanisms which control the evolutionary ancient symbiotic relationship between algae and cnidarians for the first time

When life on earth developed, symbiotic associations arose as a successful strategy millions of years ago, with which organisms of different species cooperate as a close-knit community, to gain an advantage in the struggle for survival. However, we still largely do not know why they do this, what the real benefits of such partnerships are, and which molecular mechanisms are important. Scientists from the Collaborative Research Centre (CRC) 1182 “Origin and Function of Metaorganisms” at Kiel University (CAU), together with Japanese researchers from the Okinawa Institute of Science and Technology (OIST) and Okayama University, have now presented the first comprehensive characterisation of symbiotic interactions, using the example of the cooperation between the freshwater polyp Hydra and the Chlorella algae living inside its cells. Their results have been jointly published in the current issue of the internationally-renowned scientific journal eLife.

In order to investigate the fundamental mechanisms of this symbiosis, the research team focused on the metabolic relationships between Hydra and its algae symbiont. The organisms live in a so-called photosynthetic symbiosis: the algae provide their host with certain metabolic products which they obtain from the conversion of solar energy. In return, they obtain nutrients from the polyps which they cannot acquire by themselves. “This form of coexistence between cnidarians and algae is an extreme form of symbiosis, in which the algae can no longer survive without their host. The symbiotic algae even give up parts of their own genetic information, and instead use the corresponding structures of the freshwater polyps,” explained Professor Thomas Bosch, cell and developmental biologist at the CAU and spokesperson for the CRC 1182, regarding the extent of the co-dependence between the species. The Hydra are also highly dependent on their symbionts, since the Chlorella colonisation boosts their reproductive success, so the organisms’ viability would be at a considerable disadvantage without the algae.

“Our results also show which specific tools are required at a genetic and molecular level to ensure that a durable and stable symbiosis can develop in the course of evolution,” continued Bosch. On the one hand, laboratory studies revealed that the presence of the symbionts led to significant up-regulation of certain Hydra genes responsible for the metabolism, boosting the nutrient transport between host and symbiont. On the other hand, analysis of the genome of the symbiotic algae revealed that the symbiont is missing the genetic components required to utilise nitrogen, so that the nutrient supply must be partly taken over by the host.

Overall, this new publication answers one of the most important research questions in the first funding phase of the CRC 1182: the driving forces behind the evolution and long-term stability of a symbiosis. The analysis of the interactions between Hydra polyps and algae makes it clear that the co-evolution of organisms can be driven in particular by the possibility of mutual nutrient exchange. The scientists in Kiel, together with their international colleagues, now plan to build on the results of their research and investigate more complex, multi-organismic interaction networks.

A better understanding of the symbiotic relationships between cnidarians and algae is not only valuable in terms of basic scientific knowledge gained, but can also serve as a model for the assessment of climate change, associated with the change of marine ecosystems: corals, for example, are greatly threatened by the impact of global changes since their ability to absorb nutrients is dramatically affected by changes in the nutrient content of sea water. In turn, the diverse, vibrant, tropical reef-based communities depend on the health and growth of the corals. As corals – like freshwater polyps – are dependent on certain symbiotic bacteria for their nutrient uptake, a more accurate understanding of the underlying mechanisms is required. Further research is necessary to determine whether the new knowledge gained is also applicable to the symbiosis of corals and bacteria, and if this can lead to possible future adaptation strategies for protecting endangered tropical coral reefs.

Original publication:
Mayuko Hamada, Katja Schröder, Jay Bathia, Ulrich Kürn, Sebastian Fraune, Mariia Khalturina, Konstantin Khalturin, Chuya Shinzato, Nori Satoh, Thomas C G Bosch (2018): Metabolic co-dependence drives the evolutionarily ancient HydraChlorella symbiosis eLife DOI 10.7554/eLife.35122

A photo is available for download under:

www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2018/207-hydra-chlorella.jpg
Caption: Microscopic view of Hydra-cells (nuclei appear in green) containing about 20-30 symbiotic Chlorella-algae each (in orange).
Image: Jay Bathia

Contact:
Prof. Thomas Bosch
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

More information:
Priority research area “Kiel Life Science”, Kiel University
www.kls.uni-kiel.de

eLife digest, eLife Sciences Publications

Kiel University
Press, Communication and Marketing, Dr Boris Pawlowski, Text: Christian Urban
Postal address: D-24098 Kiel, Germany, Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de, Internet: www.uni-kiel.de, Twitter: www.twitter.com/kieluni
Facebook: www.facebook.com/kieluni, Instagram: www.instagram.com/kieluni

 

How antibiotic resistance persists thanks to selfish genetic elements

Jun 13, 2019

Kiel research team shows mechanisms which enable bacteria to maintain resistance, even under non-selective conditions

 


Parts of the genetic information of many microorganisms are located on so-called plasmids. These are genetic elements which consist of a single DNA ring, and can reproduce independently of their host. Most bacteria carry plasmids as they enable them to acquire new genetic information by a process that is termed horizontal gene transfer. During this process plasmids can supply bacterial cells with novel genetic material, and also transfer it across the boundaries of other bacterial species. Thus, this process allows bacteria to quickly adapt to changing environmental conditions, which is particularly an advantage for bacterial pathogens. However, plasmids aren’t available "for free" for the host organism, as they use the host cells’ resources for their energy requirements and reproduction. Therefore, scientists have assumed that plasmids are only hosted by bacteria for as long as they can provide an evolutionary advantage. A research team from the Institute of General Microbiology at Kiel University (CAU), together with colleagues from the Israeli Ben-Gurion University of the Negev, have demonstrated that this is not always the case: Using the model organism Escherichia coli, a bacterium which frequently occurs in the intestine of various vertebrates, the scientists in a research project of the Kiel Evolution Center (KEC) were able to show that plasmids can survive permanently in bacteria, even without an apparent benefit for the host. However, in the long term, this enables bacteria to retain a potential benefit for rapid evolutionary adaptation in fluctuating environments. The Kiel research team published their findings today in the renowned journal Nature Communications.

How plasmids outlast non-selective conditions
Positive selection pressure ensures that certain plasmid functions persist when beneficial for the host. Such an external selective pressure for adaptation would be, for example, the introduction of an antibiotic. Here, the bacteria benefit from the resistance genes carried by the plasmids that provide antibiotics resistance to the cell. To date, it was assumed that plasmids are also a burden for the bacterial cell, and therefore only exist for as long as they are needed. If the bacteria are no longer exposed to the antibiotics, and therefore the selection pressure is no longer present, the plasmids should theoretically be slowly lost and become extinct.

However, as diverse plasmids are highly abundant in nature, this assumption cannot be realistic. To find out what actually happens to plasmids without selection pressure - i.e. without the antibiotics - the Kiel research team conducted an evolutionary experiment. For this purpose, the team monitored the bacterium Escherichia coli for a total of 1,000 generations. They examined how a certain plasmid - which was previously unstudied, but known to occur in numerous bacterial hosts - behaves in the absence of such selection pressure - i.e. where the host obtains no functional advantage from its existence.

"Our research results show that the frequency of plasmids decreases without antibiotics, but that they can survive at a low and stable level," explained Tanita Wein, doctoral researcher in the Genomic Microbiology working group at the CAU and first author of the study. "With these findings, we deliver a new, evolutionary explanation for the ubiquitous occurrence of plasmids in nature" said Wein.
 

An advantage for some, and a disadvantage for others
In order to also investigate the influence of environmental conditions on the survival of the plasmids, the researchers compared the effects of different ambient temperatures: on the one hand, the optimum temperature for the prosperity of the host bacteria of 37° C, and on the other hand, stress-inducing conditions of only 20° C. The results of this experiment showed that the plasmid frequency decreased slower at cold temperature compared to their preferred temperature range. Thus, the survival of plasmids in bacteria depends not only on positive selection for the plasmid function, but is also strongly influenced by the environmental conditions. "We show that unfavourable conditions for the bacteria may be favourable for the plasmid persistence as the plasmids may reproduce more efficiently," emphasised the microbiologist Wein. Therefore, the survival of the plasmids may be a process that is intrinsically controlled, and is not necessarily associated with an advantage for the organism as a whole," explained Wein.

Better understanding of the rapid spread of resistance
Another important aspect was discovered by the Kiel research team, which is also supported by the DFG priority programme (SPP) 1819 "Rapid evolutionary adaptation", when they exposed the bacteria to antibiotics after the experiment under non-selective conditions. Even a single dose caused all of the following generations of bacteria to have 100 percent resistance to the drug. In such a case, one speaks of an "evolutionary bottleneck", through which figuratively speaking only the insensitive individuals may progress. Thus, the new research findings show that in the course of evolution, the stable survival of the plasmids ensures that the antibiotic resistance of the bacteria can remain latently present, even if the bacteria had not previously come into contact with the antibiotic substance. "Our findings based on the example of a specific plasmid type therefore offer promising approaches for future research on the role of plasmids in bacterial rapid adaptation to fluctuating conditions," summarised Professor Tal Dagan, KEC member and head of the Genomic Microbiology working group.

About the KEC:
The Kiel Evolution Center (KEC) is an interactive platform at Kiel University that aims to better coordinate evolutionary researchers in Kiel and surroundings. Furthermore, under the key term of "Translational Evolutionary Research", specific bridges should be built between fundamental research and practical applications. Alongside the promotion of science, the focus of the Kiel Evolution Center also expressly includes teaching and public relations work. In addition to CAU, there are researchers involved from the Helmholtz Center for Ocean Research Kiel (GEOMAR), the Max Planck Institute for Evolutionary Biology in Plön (MPI-EB) and the Research Center Borstel (FZB), Leibniz Center for Medical and Life Sciences.

Original publication:
Tanita Wein, Nils F. Hülter, Itzhak Mizrahi, Tal Dagan (2019): Emergence of plasmid stability under non-selective conditions maintains antibiotic resistance Nature communications Published on 13 June 2019 https://doi.org/10.1038/s41467-019-10600-7

Photos are available for download at:
https://www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/190-wein-naturecomms-lab.jpg
Caption: In her doctoral research, Tanita Wein investigated how plasmids develop under non-selective conditions, using the example of the bacterium Escherichia coli.
© Institute of General Microbiology, Kiel University

https://www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/190-wein-naturecomms-group.jpg
Caption:  Some of the authors of the new research: Professor Tal Dagan (left), Tanita Wein and Dr Nils Hülter from the Institute of General Microbiology at the CAU
© Institute of General Microbiology, Kiel University


Contact:
Tanita Wein
Genomic Microbiology working group,
Institute of General Microbiology
Email: twein@ifam.uni-kiel.de
Tel.: +49 (0) 431-880-5743

Prof. Tal Dagan
Head of the Genomic Microbiology working group,
Institute of General Microbiology, Kiel University
Email: tdagan@ifam.uni-kiel.de
Tel.: +49 (0) 431-880-5712

Press contact:
Christian Urban
Scientific communication "Kiel Life Science“, Kiel University:  
Tel.: +49 (0) 431-880-1974
Email: curban@uv.uni-kiel.de

More information:
Genomic Microbiology working group,
Institute of General Microbiology, Kiel University:
https://www.mikrobio.uni-kiel.de/de/ag-dagan

Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

Priority programme (SPP) 1819 "Rapid evolutionary adaptation",
University of Hohenheim:
dfg-spp1819.uni-hohenheim.de/startseite

 

 

Coincidence or master plan?

Jun 20, 2019

- Joint press release by Kiel University and the Max Planck Institute for Evolutionary Biology in Plön -

CRC 1182 research team proposes stochastic model to explain microbiome composition

All living things - from the simplest animal and plant organisms to the human body - live closely together with an enormous abundance of microbial symbionts, which colonise the insides and outsides of their tissues. The functional collaboration of host and microorganisms, which scientists refer to as a metaorganism, has only recently come into the focus of life science research. Today we know that we can only understand many of life’s processes in connection with the interactions between organism and symbionts. The Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms” at Kiel University (CAU) aims to understand the communication and the functional consequences of host-microbe relationships.



A key issue for the researchers at the CRC 1182 is how the composition of an organism’s microbiome forms during its individual development.  It is still unclear as to whether the microbial community composition is more governed by a functional selection process or if random processes dominate.  In order to examine the microbiome composition, a research team from the CAU’s CRC 1182 and the Max Planck Institute for Evolutionary Biology in Plön (MPI-EB) has now applied the theory of the so-called “neutral metaorganism” to an entire spectrum of model organisms, from very simple creatures to complex vertebrates. The scientists from Kiel and Plön published their findings yesterday in the journal PLOS Biology.

The null model of evolutionary theory

Theoretical models offer one way to make the highly complex, individual microbiome composition manageable. A fundamental model in evolutionary research is the so-called neutral null model. This is used to predict how populations would develop without any selection pressure whatsoever. The research team at the CRC 1182 has now applied this model to several model organisms from threadworms to house mice and compared the predictions with experimentally collected data. “Theory and experimental data match surprisingly well for many organisms. The predicted composition in the house mouse, for example, is found in the actual microbial species community,” summarised Dr Michael Sieber, research associate at the MPI-EB and member of the CRC 1182. “It is possible that selection plays a lesser role in the microbiome’s composition than we previously assumed, while this does not mean that the microbiome has no important functions for the organism, it could be an indication that many different compositions of the microbiome can perform these functions equally well. And which specific composition actually forms in a single organism is then driven by chance.”

A map for further exploration of the microbiome

The researchers did notice some significant deviations between the neutral model and the real compositions of the microbiome, however. For example, individual bacterial species in the mouse microbiome did not match the neutral prediction. And the microbial species composition of the Caenorhabditis elegans thread worm did not match the neutral model at all.

“We assume that these deviations between model and reality could indicate specific functions of certain microorganisms,” Sieber emphasised. Investigating the systematic deviations from the neutral model therefore holds the potential to discover key functions of certain bacterial species within the microbiome.

First explanations for the deviations from the neutral model are already being discussed. Some non-neutral bacteria in the mouse microbiome, for example, are involved in digestion and their presence may therefore be the result of a targeted selection process. On the other hand, Caenorhabditis elegans, with its very fast generational change, might not live long enough to develop a stable, mainly neutral composition of its microbiome. “The model of the neutral metaorganism therefore provides an important theoretical basis for further functional analyses of microbiome compositions across the entire spectrum of the model organisms investigated in our Collaborative Research Centre,” said CRC 1182 spokesperson Prof. Thomas Bosch.

Original publication:
Michael Sieber, Lucía Pita, Nancy Weiland-Bräuer, Philipp Dirksen, Jun Wang, Benedikt Mortzfeld, Sören Franzenburg, Ruth A. Schmitz, John F. Baines, Sebastian Fraune, Ute Hentschel, Hinrich Schulenburg, Thomas C. G. Bosch, Arne Traulsen (2019): Neutrality in the Metaorganism. PLOS Biology Published on 19 June 2019 DOI: 10.1371/journal.pbio.3000298

Photos are available for download at:

Caption: Dr Michael Sieber (left) und Prof. Arne Traulsen, Max-Planck-Institute for Evolutionary Biology, developed the Neutral Model together with researchers of the CRC 1182.
© Christian Urban, Kiel University

Caption: The scientists applied the new theoretical approach to a range of model organisms, e.g. threadworms or mice, which are investigated in the CRC 1182 at Kiel University.
© Science Communication Lab

Contact:
Dr Michael Sieber
Evolutionary Theory Department
Max Planck Institute for Evolutionary Biology in Plön
Tel.: +49 (0)4522 763-579
E-mail: sieber@evolbio.mpg.de
   
Prof. Arne Traulsen
Evolutionary Theory Department
Max Planck Institute for Evolutionary Biology in Plön
Tel.: +49 (0)4522 763-239
E-mail: traulsen@evolbio.mpg.de

Prof. Thomas Bosch,
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

Press contact:
Christian Urban
Science communication “Kiel Life Science”   
Tel.: +49 (0)431-880-1974
E-mail: curban@uv.uni-kiel.de

More information:
Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

Evolutionary Theory Department,
Max Planck Institute for Evolutionary Biology in Plön:
http://web.evolbio.mpg.de/~traulsen/#home

AG Bosch, Kiel University:
http://www.bosch.zoologie.uni-kiel.de/
 

 

 

 

Over-fed bacteria make people sick

May 15, 2019

In a new hypothesis, a CRC 1182 research team suggests that inflammatory diseases are caused by an over-supply of food, and the associated disturbance of the intestine’s natural bacterial colonisation.  

Since the end of the Second World War, along with the growing prosperity and the associated changes in lifestyle, numerous new and civilisation-related disease patterns have developed in today's industrialised nations. Examples of the so-called "environmental diseases" are different bowel inflammations like Crohn's disease or ulcerative colitis. Common causes include disruptions to the human microbiome, i.e. the natural microbial colonisation of the body, and in particular of the intestine. To date, scientists have explained this disrupted cooperation between host body and microbes with different hypotheses: for example, they postulated that excessive hygiene, the intensive use of antibiotics, or certain genetic factors permanently disrupt the microbiome, thus making people vulnerable to illnesses. However, these explanation attempts have so far been incomplete. A team from the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms” at Kiel University (CAU) has now formulated a new and more comprehensive ecological-evolutionary theory on the development of environmental diseases. The Kiel researchers suggest that an unnatural and particularly comprehensive nutrient supply decouples bacteria from their host organisms, and thus destroys the delicate balance of the microbiome. The, to some extent, over-fed bacteria in the gut thus promote disease development. The Kiel scientists published this fundamental new approach towards a more complete explanation of environmental diseases yesterday in the journal mBio.


The origin lies in the oceans

The starting point for the Kiel research team was the ecology of marine habitats: research on coral and algae dying off, and the associated effects on important ecosystems in the oceans, suggests that in addition to other factors such as climate change or overfishing, the nutrient conditions in the seawater may be the cause of the problem. As soon as there is an oversupply of food due to human influences, bacteria living in a community with corals begin to decouple from their hosts. They then no longer feed off the metabolic products of the host, but prefer the richer nutrient supply of the surrounding waters. The balance of the coral microbiome is disrupted because of the exodus of its symbiotic partner, and diseases occur as a result. "In this connection between nutrient availability and the balance of bacteria-host relationships, we see a universal principle which goes way beyond the very specific example of corals," explained Dr Tim Lachnit, research associate at the CRC 1182 and first author of the study. "In studies of our model organism, the freshwater polyp Hydra, we were able to experimentally confirm this connection," continued Lachnit. These small cnidarians also showed clear signs of disease as soon as their normal nutrient uptake was disturbed and an over-supply of food was available instead.

What do corals and cnidarians have to do with people?

With a high degree of probability, the knowledge gained in the experiment can also be transferred to human health. Similar to in seawater, or in the simple body cavity of a freshwater polyp, which during the course of evolution has decoupled from its external environment and a direct food supply, the nutrient supply in the human gut is also changing along with the civilisation-induced changes in eating habits - towards an unbalanced, energy-rich and low-fibre diet. In addition to direct negative health consequences, a permanently high, easy to process supply of nutrients not only affects the human metabolism it feeds, but also the bacterial colonisation of the intestine, which is also "fed". The microbes switch from the metabolites of the host as their staple food to the abundantly available nutrients from the human food and thus decouple from their interactions with the host organism. "This over-feeding of the bacteria promotes their growth as a whole, and certain species of bacteria proliferate to the detriment of other members of the microbiome in an increased and uncontrolled manner," emphasised Professor Thomas Bosch, spokesperson of the CRC 1182. "Thus, along with the change in the composition of the bacterial colonisation, the interactions between bacteria and host organism also change, and a serious maladaptation - known as dysbiosis - occurs," explained Dr Peter Deines, research associate at the Kiel metaorganism CRC.

Other civilisation-related factors increase this imbalance of the microbiome. The elimination of periodic fasting resulting from food sources not always being available, the only very rare occurrence of diarrhoea leading to episodic reductions of the intestinal bacterial colonisers and the diet-related impoverishment of the microbial diversity in the gut are just a few examples. The first two of these represent very fundamental mechanisms, which since the early development of mankind right up to the pre-industrial era enabled the microbiome to return to a normal state at regular intervals, and thus regain a healthy and natural composition.

Does the microbiome heal itself?

The "over-feeding hypothesis" proposed by researchers from the Kiel CRC 1182, in close cooperation with the CAU Cluster of Excellence "Precision Medicine in Chronic Inflammation", offers valuable approaches for further research, right through to potential transfer to future treatments: to date, scientists were particularly looking for ways to correct a disturbed microbiome through external interventions such as probiotics, i.e. the addition of certain types of helpful bacteria, or even faecal transplants to restore the balance. Now, the ecological-evolutionary perspective has added another dimension. More than ever before, it incorporates the natural ability of the microbiome to readjust itself, and to restore a healthy composition. Therefore, future research approaches lie in the specific mechanisms that balance the microbiome, and the question of whether the "overfeeding" of the bacteria can be reduced by changed eating habits. "An interesting question will be whether the original evolutionary processes which ensure the balance of the microbiome also have therapeutic potential," said Lachnit. "In the future we will, for example, not only consider the known health benefits of fasting, but also its effects on the composition and function of the microbiome, and thus on the development of inflammatory diseases," continued Lachnit.

Original publication:
Tim Lachnit, Thomas CG Bosch & Peter Deines (2019): Exposure of the host-associated microbiome to nutrient-rich conditions may lead to dysbiosis and disease development – an evolutionary perspective. mBio Published on May 14, 2019
DOI: 10.1128/mBio.00355-19

Photos are available for download under:
Caption: The fresh water polyp Hydra as a model system shows possible links between overfed microbes and the development of disease.
© Kiel Life Science

Caption: CRC 1182 researchers Dr Tim Lachnit (left) und Dr Peter Deines investigated the connections between nutrient availability and the balance of the microbiome.
© Christian Urban, Kiel University

Contact:
Dr Tim Lachnit
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4171
E-mail: tlachnit@zoologie.uni-kiel.de

Prof. Thomas Bosch
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

Dr Peter Deines
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4171
E-mail: pdeines@zoologie.uni-kiel.de

Press contact:
Christian Urban
Science communication “Kiel Life Science”   
Tel.: +49 (0)431-880-1974
E-mail: curban@uv.uni-kiel.de

More information:
AG Bosch, Kiel University:
www.bosch.zoologie.uni-kiel.de/

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com


 

 

Why are we different sizes?

Sep 03, 2019

Kiel research team describes the interplay of environmental factors and internal regulation in determining the growth of an organism

The body size of a living creature has a direct impact on its fitness - from the simplest animal and plant organisms right up to human beings. The individual size or height is therefore an important criterion for the ability of an organism to succeed in the competition for resources or reproduction. We basically assume that there is similar genetic information within a species, which in theory should lead to relatively uniform body sizes. However, within specific physiological limits, the individuals of most species grow to very different sizes - thus size must also be dependent on other factors. But precisely which parameters regulate growth at the molecular level has hardly been investigated to date. Now, scientists from the Zoological Institute at Kiel University (CAU) have been able to show how environmental factors and internal regulatory processes jointly control body growth, using the example of the freshwater polyp Hydra. The Kiel researchers demonstrated that the ambient temperature activates specific molecular signalling pathways of the growth process, and is thus involved in determining size. In addition, they showed that genetic factors also utilise identical signal pathways, likewise contributing to size regulation in the cnidarians. The Kiel research team recently published their new findings in the renowned scientific journal Nature Communications.

Interplay of environmental and internal regulation
From a cellular biological perspective, the size of a fully-grown organism is the result of three variables: the duration of its growth, the absolute number of the resulting cells and the individual size of all these cells, which together make up the mature organism. In the course of this characteristic growth process, the organism must be able to measure its current size, and the attainment of its maximum size. In their study, the CAU researchers initially focused on the regulation of the number of cells of the cnidarian Hydra.

"We observed that Hydra produces up to 83 percent more cells at low ambient temperatures," explained Dr Jan Taubenheim, whose doctoral research in the field of cellular and developmental biology was incorporated in the current publication. "We also managed to identify the specific molecular signalling pathways which implement the influence of the temperature on the number of cells, and thus produce larger animals at cooler temperatures," emphasised Taubenheim, who is now a research associate at the Heinrich Heine University Düsseldorf. These so-called Wnt and TGF-beta signals are involved, for example, in embryonic development and cell differentiation. Their interaction with the ambient temperature and growth in size was previously unknown. "The Wnt signals also determine the transition from growth to a stationary phase in Hydra. Therefore, we suspect that they serve the organism as a measuring instrument to determine its own size, before it stops growing," said Dr Benedikt Mortzfeld, who also obtained his doctorate in cellular biology at the CAU, and is currently employed as a research scientist at the University of Massachusetts Medical School in Worcester.

The influence of genes
In addition to the ambient temperature, certain genetic information also contribute to size regulation in cnidarians. Genes that are responsible for the so-called insulin signalling pathway jointly determine the growth, among other things by controlling the number of cells during the growth phase. In a functional gene analysis, the Kiel research team was also able to show that switching off the genes responsible for this signalling pathway led to body sizes up to 41 percent smaller in the polyps. Thus, an important role in the cellular regulation processes of growth is also played by the genetic information. "Environmental factors and genetic factors take effect one after another in a multi-step process, in a fixed hierarchical sequence, and rely on the same cellular regulatory mechanisms," summarised Professor Thomas Bosch, spokesperson of the CAU Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms". "Thus they together control cell number and size as well as the duration of the growth phase, and through their interplay facilitate great variability, which results in very different body sizes of the adult organisms," continued Bosch.

Size regulation - a common principle?
The new findings on regulating size growth in the model organism Hydra contribute towards identifying universal principles in multicellular organisms. Certain similarities in the signalling pathways lead the researchers to suspect that different organisms incorporate the influences of environment and genetics in a very similar way in their internal size regulation. The next important step will be to also investigate the influence of bacterial colonisation of the body on the underlying control processes. "We suspect that the symbiotic microorganisms of the body are also inextricably linked with the regulation of individual development and thus growth in size of an organism," said Bosch. In future, the scientists want to examine this possible involvement more closely in the framework of the CRC 1182, in order to gain a better understanding of size regulation in organisms, summarised Bosch.

Original publication:
Benedikt M. Mortzfeld*, Jan Taubenheim*, Alexander V. Klimovich, Sebastian Fraune, Philip Rosenstiel & Thomas C. G. Bosch (2019): Temperature and insulin signaling regulate body size in Hydra by the Wnt and TGF-beta pathways.
Nature Communications Published on 22 July 2019
DOI: doi.org/10.1038/s41467-019-11136-6
*Authors contributed equally

A photos is available for download at:
www.uni-kiel.de/de/pressemitteilungen/2019/261-mortzfeld-ncomms.jpg
Caption: Some specimens of the cnidarian Hydra demonstrating the effects of environmental factors and internal regulation on body growth.
© Dr. Benedikt Mortzfeld

Contact:
Prof. Thomas Bosch,
Zoological Institute, Kiel University
Tel.: +49 (0)431-880-4170
E-mail: tbosch@zoologie.uni-kiel.de

Press contact:
Christian Urban
Science communication “Kiel Life Science”, Kiel University  
Tel.: +49 (0)431-880-1974
E-mail: curban@uv.uni-kiel.de

More information:
AG Bosch, Kiel University:
www.bosch.zoologie.uni-kiel.de

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

How antibiotic resistance persists thanks to selfish genetic elements

Jun 13, 2019

Kiel research team shows mechanisms which enable bacteria to maintain resistance, even under non-selective conditions

 


Parts of the genetic information of many microorganisms are located on so-called plasmids. These are genetic elements which consist of a single DNA ring, and can reproduce independently of their host. Most bacteria carry plasmids as they enable them to acquire new genetic information by a process that is termed horizontal gene transfer. During this process plasmids can supply bacterial cells with novel genetic material, and also transfer it across the boundaries of other bacterial species. Thus, this process allows bacteria to quickly adapt to changing environmental conditions, which is particularly an advantage for bacterial pathogens. However, plasmids aren’t available "for free" for the host organism, as they use the host cells’ resources for their energy requirements and reproduction. Therefore, scientists have assumed that plasmids are only hosted by bacteria for as long as they can provide an evolutionary advantage. A research team from the Institute of General Microbiology at Kiel University (CAU), together with colleagues from the Israeli Ben-Gurion University of the Negev, have demonstrated that this is not always the case: Using the model organism Escherichia coli, a bacterium which frequently occurs in the intestine of various vertebrates, the scientists in a research project of the Kiel Evolution Center (KEC) were able to show that plasmids can survive permanently in bacteria, even without an apparent benefit for the host. However, in the long term, this enables bacteria to retain a potential benefit for rapid evolutionary adaptation in fluctuating environments. The Kiel research team published their findings today in the renowned journal Nature Communications.

How plasmids outlast non-selective conditions
Positive selection pressure ensures that certain plasmid functions persist when beneficial for the host. Such an external selective pressure for adaptation would be, for example, the introduction of an antibiotic. Here, the bacteria benefit from the resistance genes carried by the plasmids that provide antibiotics resistance to the cell. To date, it was assumed that plasmids are also a burden for the bacterial cell, and therefore only exist for as long as they are needed. If the bacteria are no longer exposed to the antibiotics, and therefore the selection pressure is no longer present, the plasmids should theoretically be slowly lost and become extinct.

However, as diverse plasmids are highly abundant in nature, this assumption cannot be realistic. To find out what actually happens to plasmids without selection pressure - i.e. without the antibiotics - the Kiel research team conducted an evolutionary experiment. For this purpose, the team monitored the bacterium Escherichia coli for a total of 1,000 generations. They examined how a certain plasmid - which was previously unstudied, but known to occur in numerous bacterial hosts - behaves in the absence of such selection pressure - i.e. where the host obtains no functional advantage from its existence.

"Our research results show that the frequency of plasmids decreases without antibiotics, but that they can survive at a low and stable level," explained Tanita Wein, doctoral researcher in the Genomic Microbiology working group at the CAU and first author of the study. "With these findings, we deliver a new, evolutionary explanation for the ubiquitous occurrence of plasmids in nature" said Wein.
 

An advantage for some, and a disadvantage for others
In order to also investigate the influence of environmental conditions on the survival of the plasmids, the researchers compared the effects of different ambient temperatures: on the one hand, the optimum temperature for the prosperity of the host bacteria of 37° C, and on the other hand, stress-inducing conditions of only 20° C. The results of this experiment showed that the plasmid frequency decreased slower at cold temperature compared to their preferred temperature range. Thus, the survival of plasmids in bacteria depends not only on positive selection for the plasmid function, but is also strongly influenced by the environmental conditions. "We show that unfavourable conditions for the bacteria may be favourable for the plasmid persistence as the plasmids may reproduce more efficiently," emphasised the microbiologist Wein. Therefore, the survival of the plasmids may be a process that is intrinsically controlled, and is not necessarily associated with an advantage for the organism as a whole," explained Wein.

Better understanding of the rapid spread of resistance
Another important aspect was discovered by the Kiel research team, which is also supported by the DFG priority programme (SPP) 1819 "Rapid evolutionary adaptation", when they exposed the bacteria to antibiotics after the experiment under non-selective conditions. Even a single dose caused all of the following generations of bacteria to have 100 percent resistance to the drug. In such a case, one speaks of an "evolutionary bottleneck", through which figuratively speaking only the insensitive individuals may progress. Thus, the new research findings show that in the course of evolution, the stable survival of the plasmids ensures that the antibiotic resistance of the bacteria can remain latently present, even if the bacteria had not previously come into contact with the antibiotic substance. "Our findings based on the example of a specific plasmid type therefore offer promising approaches for future research on the role of plasmids in bacterial rapid adaptation to fluctuating conditions," summarised Professor Tal Dagan, KEC member and head of the Genomic Microbiology working group.

About the KEC:
The Kiel Evolution Center (KEC) is an interactive platform at Kiel University that aims to better coordinate evolutionary researchers in Kiel and surroundings. Furthermore, under the key term of "Translational Evolutionary Research", specific bridges should be built between fundamental research and practical applications. Alongside the promotion of science, the focus of the Kiel Evolution Center also expressly includes teaching and public relations work. In addition to CAU, there are researchers involved from the Helmholtz Center for Ocean Research Kiel (GEOMAR), the Max Planck Institute for Evolutionary Biology in Plön (MPI-EB) and the Research Center Borstel (FZB), Leibniz Center for Medical and Life Sciences.

Original publication:
Tanita Wein, Nils F. Hülter, Itzhak Mizrahi, Tal Dagan (2019): Emergence of plasmid stability under non-selective conditions maintains antibiotic resistance Nature communications Published on 13 June 2019 https://doi.org/10.1038/s41467-019-10600-7

Photos are available for download at:
https://www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/190-wein-naturecomms-lab.jpg
Caption: In her doctoral research, Tanita Wein investigated how plasmids develop under non-selective conditions, using the example of the bacterium Escherichia coli.
© Institute of General Microbiology, Kiel University

https://www.uni-kiel.de/fileadmin/user_upload/pressemitteilungen/2019/190-wein-naturecomms-group.jpg
Caption:  Some of the authors of the new research: Professor Tal Dagan (left), Tanita Wein and Dr Nils Hülter from the Institute of General Microbiology at the CAU
© Institute of General Microbiology, Kiel University


Contact:
Tanita Wein
Genomic Microbiology working group,
Institute of General Microbiology
Email: twein@ifam.uni-kiel.de
Tel.: +49 (0) 431-880-5743

Prof. Tal Dagan
Head of the Genomic Microbiology working group,
Institute of General Microbiology, Kiel University
Email: tdagan@ifam.uni-kiel.de
Tel.: +49 (0) 431-880-5712

Press contact:
Christian Urban
Scientific communication "Kiel Life Science“, Kiel University:  
Tel.: +49 (0) 431-880-1974
Email: curban@uv.uni-kiel.de

More information:
Genomic Microbiology working group,
Institute of General Microbiology, Kiel University:
https://www.mikrobio.uni-kiel.de/de/ag-dagan

Research centre “Kiel Evolution Center”, Kiel University:
www.kec.uni-kiel.de

Priority programme (SPP) 1819 "Rapid evolutionary adaptation",
University of Hohenheim:
dfg-spp1819.uni-hohenheim.de/startseite

 

 

Did microbes assist life in colonizing land?

Sep 19, 2019

Comparative microbiome study enables researchers of the Kiel based CRC 1182 to gain new insights into the course of evolution

All living organisms exist and function only in cooperation with an abundance of symbiotic microorganisms, and have developed together with them over the course of the earth's history. This central finding of modern life sciences has led researchers worldwide to analyse the highly complex interactions and long-term bonds of host organisms and microbes in ever greater detail. Gradually, they want to achieve a new functional understanding of biology and the development of life. In the analysis of the complex interactions within the so-called metaorganism, the unit consisting of a body and the totality of its microbial colonisation, in short the microbiome, scientists use techniques such as genome sequencing. These technologies make it possible to analyse genetic information from large quantities of biological sample material and, thanks to new high-throughput methods, quickly assign it to specific organisms and, in some cases, to possible functions.

Scientists from all working groups at Kiel University involved in the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms" have now compared various sequencing techniques in an extensive comparative study using various model organisms: On the one hand to assess their optimal areas of application, and on the other hand to identify possible similarities between different multicellular host organisms and their microbiomes. A surprising result of the study presented here is that organisms living on land generally have a significantly different microbiome than species living in water. The researchers interpret this as an indication that microorganisms may have played a key role in the evolutionary transition from purely aquatic life to life on land. The new research results were published last week in the renowned scientific journal Microbiome.

The microbiome and adaptation to terrestrial life
In the new study, the scientists of the CRC 1182 used the opportunity to compare the microbiomes of many different model organisms - from simple sponges to vertebrates, including humans. They examined sample material from the various subprojects of the collaborative research project for patterns in the composition of microbial communities and compared different methods of the two most important sequencing technologies. By chance, they came across an interesting observation: the microbiome of terrestrial organisms, regardless of their kinship relationships, differs significantly from those of aquatic organisms - in which all analytical techniques coincided. Terrestrial organisms have a lower diversity of microorganisms contained in their microbiome.

A possible explanation for the differences in the composition of the microbiome could be that former aquatic organisms were forced to acquire new microbial communities upon the colonisation of the land. The transition from water to land, which began about 500 million years ago, might have been dependent on a change in the microbiome. "Just as adaptation to life on land brought about gradual, but massive morphological changes, such changes apparently also took place in the terrestrial host-associated microbiome," says John Baines, Professor for Evolutionary Genomics at Kiel University. "In order to cope with the new environmental conditions, living organisms may have resorted to terrestrially adapted microbes to maintain their vital functions," Baines continues.

Choosing the right tool
In addition to these revealing findings on a possible influence of microbiota on the course of evolution, the new CRC 1182 study also provides an aid in choosing the appropriate analytical method for the investigation of a given microbial community. On the one hand, certain sequencing methods provide only a rough identity of the microorganisms present in a sample. These comparatively inexpensive methods - such as the so-called '16s rRNA gene amplicon' method - use individual marker genes from which it is possible to deduce the associated living organisms.

More complex methods such as the so-called 'metagenomic shotgun' sequencing make it possible to record and evaluate all the genetic information in a sample. For example, they can identify individual bacterial species within the microbiome and are also able to deduce microbial functions. In comparison, however, they are more cost-intensive, their informative value depends more on the specific field of application and they are therefore currently less standardised than simpler methods.

New insights into the course of evolution
In the future, the Kiel researchers, together with their international colleagues, want to understand more precisely what role microorganisms played in the transition from an aquatic to a terrestrial way of life over the course of earth's history. "There are many indications that symbiotic microorganisms have also played a role in major evolutionary transitions," stresses CRC 1182 spokesperson Professor Thomas Bosch. "It is therefore our goal to identify the specific evolutionary mechanisms that caused the diversification of the microbiome parallel to the colonization of the land," continues Bosch.

Original publication:
Philipp Rausch, Malte Rühlemann, Britt M. Hermes, Shauni Doms, Tal Dagan, Katja Dierking, Hanna Domin, Sebastian Fraune, Jakob von Frieling, Ute Hentschel, Femke-Anouska Heinsen, Marc Höppner, Martin T. Jahn, Cornelia Jaspers, Kohar Annie B. Kissoyan, Daniela Langfeldt, Ateeqr Rehman, Thorsten B. H. Reusch, Thomas Roeder, Ruth A. Schmitz, Hinrich Schulenburg, Ryszard Soluch, Felix Sommer, Eva Stukenbrock, Nancy Weiland-Bräuer, Philip Rosenstiel, Andre Franke, Thomas Bosch, John F. Baines (2019): Comparative analysis of amplicon and metagenomic sequencing methods reveals key features in the evolution of animal metaorganisms. Microbiome Published on September 14, 2019
DOI: 10.1186/s40168-019-0743-1

Photos are available for download at:
www.uni-kiel.de/de/pressemitteilungen/2019/272-rausch-microbiome-crcmembers.JPG
Caption: Scientists from all working groups involved in the CRC 1182 contributed to the comprehensive study.
© Christian Urban, Kiel University

www.uni-kiel.de/de/pressemitteilungen/2019/272-rausch-microbiome-modelorganisms.jpg
Caption: The Kiel based researchers compared the microbiome data of many different model organisms - from simple sponges to vertebrates including humans.
© Science Communication Lab

www.uni-kiel.de/de/pressemitteilungen/2019/272-rausch-microbiome-baines.jpg
Caption: John Baines, Professor for Evolutionary Genomics at Kiel University, led the comparative microbiome study of the Collaborative Research Centre.
© Christian Urban, Kiel University

Contact:
Prof. John Baines
Institute for Experimental Medicine, Kiel University
Tel.: +49 (0) 431-500-30310
E-Mail: j.baines@iem.uni-kiel.de

Press contact:
Christian Urban
Science communication “Kiel Life Science”, Kiel University   
Tel.: +49 (0) 431-880-1974
E-Mail: curban@uv.uni-kiel.de

More Informationen:
Research Group Evolutionary Genomics, Max-Planck-Institute for Evolutionary Biology, Plön /
Kiel University:
web.evolbio.mpg.de/evolgenomics/index.html

Collaborative Research Centre 1182 „Origin and Function of Metaorganisms“, Kiel University:
www.metaorganism-research.com
 

 

 

 

Symbiosis as a tripartite relationship

Sep 26, 2019

- Joint press release by Kiel University and the GEOMAR Helmholtz Centre for Ocean Research Kiel -

Investigation of viral communities of sponges allows new insights into the mechanisms of symbiosis

Sponges form an extensive animal phylum with over 7,500 species worldwide, which occur in a wide range of habitats in the ocean. A special feature of this animal phylum is their ability to filter seawater, through which these organisms obtain their food. In doing so, certain sponge species can move up to 24,000 litres through their body per day. The surrounding seawater contains a wide range of viruses - on average, one millilitre of water contains 10 million viruses. The filter-feeding lifestyle of sponges combined with the rich proliferation of viruses in the ocean therefore might suggest that marine sponges may have a similar viral composition as the surrounding water.

Researchers from the Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms" at Kiel University (CAU) and the GEOMAR Helmholtz Centre for Ocean Research Kiel have now surprisingly shown that sponges possess a very specific viral sequence signature (i.e., virome), which is remarkably unique even for the individuals of a given species. Certain bacteriophages - i.e. viruses that attack bacteria - are further able to modulate the host immune system and thus protect bacterial symbionts from being digested. While viruses are typically known for their pathogenic properties, the new research findings now also demonstrate a positive influence of bacteriophages on the interaction of host organisms with bacteria. The results were obtained through international cooperation between three countries, including researchers at the universities of Würzburg, Barcelona and Utrecht. The study published today in the renowned journal Cell Host & Microbe thus sheds new light on the symbiosis between multicellular organisms and their microbial communities, which may be regulated by bacteriophages in a tripartite relationship.

An unexplored microcosm
In order to analyse the composition of the viral community of sponges, the researchers examined four different sponge species from a defined location in the Mediterranean Sea. In each case, they compared numerous individuals and different tissues of the same species with each other. "Contrary to our original assumption, each sponge individual has its own unique virome even when living right next to each other”. Therefore, no two sponges are alike with regard to their viral community," summarised Martin T. Jahn, a doctoral researcher at GEOMAR and early career researcher at the CRC 1182. "The composition of the virome is thus not primarily determined by the environment or the exposure of the tissue to the surrounding water, but is rather defined by internal factors," said the first author of the study, who collaborated with other early career researchers from four working groups at the CRC 1182.

Notably, the viruses discovered in sponges were largely unknown. "We have found almost 500 new genera of viruses in our samples," emphasised Jahn. "These viruses are completely new, and possibly only occur in sponge, and nowhere else in nature," said Jahn. This order of magnitude shows that the study of viral diversity is only just beginning.
The animal host, bacteria and phages interact with each other
The observed differences between the viral communities of sponges and those from seawater provoked the question whether sponge viruses have specific functions. The researcher team investigated the viral gene inventories and discovered genes which are similar to those of multicellular organisms, where they are responsible for interactions of certain proteins. "This surprising result awakened our special interest," said Ute Hentschel Humeida, CRC 1182 member and professor of marine microbiology at GEOMAR. "We wanted to understand why the bacteriophages have a gene encoding a protein, which we would rather expect in multicellular organisms", continued Hentschel Humeida.

In order to investigate the role of this so-called ANKp protein, they examined its impact in a model system: they expressed the protein in the bacterium Escherichia coli and investigated its effect on certain scavenger cells (macrophages) that occur in the immune system of vertebrates. The result points to a central role of the ANKp protein: it caused E. coli to be significantly less destroyed by the scavenger cells. Strikingly, the protein apparently enables the bacteriophages to interact with the animal host in that it downregulates the host’s immune response, thereby protecting the bacteria from being digested. Therefore, the scientists suggest that bacteriophages are part of a tripartite interaction of host organism, bacteria and bacteriophages, where they provide mechanisms for maintaining symbiotic co-existence.

Extension of the symbiosis concept?
The researchers at the CRC 1182 interpret the new results as a novel and important contribution of bacteriophages to the symbioses of multicellular host organisms and their microbial partners. "We suspect that bacteriophages are major players in the interaction between multicellular host organisms - including humans - and bacteria," summarised Martin T. Jahn. "Viral proteins such as ANKp may even enable this interplay of hosts and bacteria in the first place, because they allow the bacteria to evade the immune system of the host," continued Jahn. "The fundamental concept of symbiosis can therefore be understood as an interaction between three parties," concluded Hentschel Humeida. In the future, Hentschel Humeida and team will further investigate this hypothesis, which is of central importance for metaorganism research, and confirm the functional participation of bacteriophages in host-microbe symbioses.

Original publication:
Martin T. Jahn, Ksenia Arkhipova, Sebastian M. Markert, Christian Stigloher, Tim Lachnit, Lucia Pita, Anne Kupczok, Marta Ribes, Stephanie T. Stengel, Philip Rosenstiel, Bas E. Dutilh & Ute Hentschel (2019): A phage protein aids bacterial symbionts in eukaryote immune evasion. Cell Host & Microbe Published on 24 September 2019
DOI: 10.1016/j.chom.2019.08.019

Photos are available for download at:
www.uni-kiel.de/de/pressemitteilungen/2019/283-jahn-cell-hm-sponge.jpg
Caption: The three-dimensional representation of the sponge tissue illustrates the close contact of sponge cells (red) with the bacteria (turquoise) living in the sponge.
© Martin T. Jahn, GEOMAR

www.uni-kiel.de/de/pressemitteilungen/2019/283-jahn-cell-hm-author.jpg
Caption: First author Martin Jahn, doctoral researcher at GEOMAR, examined viral composition of sponges and their participation in symbiotic interactions within the framework of the CRC 1182.
© Erik Borchert, GEOMAR

www.uni-kiel.de/de/pressemitteilungen/2019/283-jahn-cell-hm-group.jpg
Caption: Some of the CRC 1182 junior researchers that cooperated in the publication: Stephanie T. Stengel (Kiel University), Martin T. Jahn (GEOMAR), Dr. Lucia Pita (GEOMAR), Dr. Tim Lachnit (Kiel University, left to right).
© Christian Urban, Kiel University


Contact:
Prof. Ute Hentschel Humeida
Research Unit Marine Symbioses
Research Division 3: Marine Ecology
GEOMAR Helmholtz Centre for Ocean Research Kiel
Tel.: +49 (0)431 600-4480
E-mail: uhentschel@geomar.de

Martin T. Jahn
Research Unit Marine Symbioses
Research Division 3: Marine Ecology
GEOMAR Helmholtz Centre for Ocean Research Kiel
Tel.: +49 (0)431 600-4486
E-mail: mjahn@geomar.de; twitter: @martintjahn

Press contact:
Christian Urban
Science communication “Kiel Life Science"
CAU Kiel
Tel.: +49 (0)431-880-1974
E-mail: curban@uv.uni-kiel.de

More information:
Research Unit Marine Symbioses,
Research division 3: Marine Ecology
GEOMAR Helmholtz Centre for Ocean Research Kiel
www.geomar.de/de/forschen/fb3/fb3-ms/schwerpunkte/

Collaborative Research Centre (CRC) 1182 "Origin and Function of Metaorganisms", Kiel University:
www.metaorganism-research.com

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